title: Pharmacy Emergency Preparedness and Response (PEPR) framework for expanding pharmacy professionals’ roles and contributions to emergency preparedness and response during the COVID-19 pandemic and beyond

text: Abstract Background Pharmacists have long been involved in public health and emergency preparedness and response (EP&R), including through preventive measures such as screening, vaccinations, testing and pharmaceutical countermeasures, as well as ensuring medication safety and access during natural disasters and pandemics. Pharmacy professionals are considered essential partners in response to the ongoing COVID-19 pandemic. Community and hospital pharmacies are expanding services and hours to provide essential services, putting pharmacists and their co-workers at the frontlines for patient care and safety to improve public health. In addition, pharmacy professionals are increasingly integrating into global, national, state and local EP&R efforts, including into interprofessional teams, such as Medical Reserve Corps (MRCs). However, lacunae exist for further integration of pharmacists into public health and safety initiatives. There are increasing opportunities and recommendations that should be expanded upon to provide improved patient care and population health intervention, and to ensure healthcare worker and public health safety. Objective Develop a Pharmacy Emergency Preparedness and Response (PEPR) Framework and recommendations for pharmacy professional pathways towards full integration within public health EP&R efforts (such as the COVID-19 pandemic), and enhanced recognition of pharmacists’ skills, roles and contributions as integral members of the interprofessional healthcare team. Methods This paper draws on the American Society of Health-System Pharmacists (ASHP) 2003 Statement on the Role of Health-System Pharmacists in Emergency Preparedness and lessons learned from previous and current public health emergencies, such as the 2009 H1N1 pandemic and the current COVID-19 pandemic, to provide expanded guidance for pharmacists and pharmacy professionals across all practice settings in EP&R. The PEPR framework also incorporates information and recommendations from The Pharmacy Organizations’ Joint Policy Recommendations to Combat the COVID-19 Pandemic (March 2020), CDC-NIOSH, Health Departments and Emergency Preparedness guidance and resources, Boards of Pharmacy, and other pharmacy professional organizations and educational institutions. Results Based on the methods and resources utilized in developing this PEPR framework, five key focus areas were identified as follow: 1) Emergency preparedness and response 2) Operations management 3) Patient care and population health interventions 4) Public health pharmacy education and continuing professional education 5) Evaluation, research and dissemination for impact and outcomes Conclusion and Recommendations: Pharmacists and pharmacy professionals have been at the frontlines in responding to the COVID-19 pandemic. Yet, challenges remain, such as limited availability of personal protection equipment, high risk of infectious exposures inherent in healthcare professions, and legislative hurdles resulting in lack of provider status and related reimbursements. Recommendations to enhance pharmacy's scope as public health professionals involved in EP&R include targeted training and education on key framework areas and policymaking. Pharmacy professionals should further integrate with interdisciplinary public health teams. Additional research and dissemination on impacts and outcomes of EP&R can enhance recognition of pharmacy professionals' contribution and value during public health emergencies. The PEPR Framework can be utilized to develop, implement, evaluate, and disseminate results in order to strengthen existing efforts and to establish new initiatives in EP&R.


title: Animal Models of Demyelination

text: Demyelination is a pathological feature that is characteristic of many diseases of the central nervous system (CNS) including multiple sclerosis (MS), sub‐acute sclerosing panencephalomyelitis (SSPE), metachromatic leukodystrophy and Pelizaeus‐Merzbacher disease. While demyelination is a pathological end‐point that is common to all of these diseases, the cellular and molecular mechanisms responsible for this pathology are very different. These range from genetic defects that affect lipid metabolism in the leukodystrophies, cytopathic effects of viral infection in SSPE to the action of immunological effector mechanisms in MS and the viral encephalopathies. Irrespective of the initial cause of myelin degradation, many of these disorders are associated with some degree of CNS inflammation, as indicated by the local activation of microglia, recruitment of macrophages or the intrathecal synthesis of immunoglobulin. Many of these phenomena are now being duplicated in animal models, providing not only new insights into the pathogenesis of human demyelinating diseases, but also unexpected interrelationships between the immune response in the CNS and the pathogenesis of diseases such as Alzheimers disease and HIV encephalopathy. Autoimmune mediated models of inflammatory demyelinating CNS disease have proved particularly valuable in this respect as they allow the effects of defined immune effector mechanisms to be studied in the absence of CNS infection.


title: Psychological Responses to Outbreak of Severe Acute Respiratory Syndrome: A Prospective, Multiple Time‐Point Study

text: Abstract This study examined anxiety and coping responses to the outbreak of severe acute respiratory syndrome (SARS) in Hong Kong. Trait anxiety, situation‐specific coping strategies, and coping flexibility were proposed as predictors of state anxiety during the early phase of the SARS epidemic. Seven‐two Hong Kong undergraduates (31 men, 41 women) participated in a prospective, multiple time‐point study. Participants' trait anxiety and coping flexibility had been assessed in an earlier study. Five months later, they reported their anxiety and coping at each of the four time points during the outbreak. Results revealed fluctuations in state anxiety across time points. Results from hierarchical linear modeling showed that trait anxiety as well as the situation‐appropriate coping strategies of avoidance and personal hygiene practice accounted for changes in state anxiety.


Taipei Azalea – Supraglottic airways (SGA) preassembled with high-efficiency particulate air (HEPA) filters to simplify prehospital airway management for patients with out-of-hospital cardiac arrests (OHCA) during Coronavirus Disease 2019 (COVID-19) pandemic


title: Identification of natural compounds with antiviral activities against SARS-associated coronavirus

text: Abstract More than 200 Chinese medicinal herb extracts were screened for antiviral activities against Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV) using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay for virus-induced cytopathic effect (CPE). Four of these extracts showed moderate to potent antiviral activities against SARS-CoV with 50% effective concentration (EC50) ranging from 2.4±0.2 to 88.2±7.7μg/ml. Out of the four, Lycoris radiata was most potent. To identify the active component, L. radiata extract was subjected to further fractionation, purification, and CPE/MTS assays. This process led to the identification of a single substance lycorine as an anti-SARS-CoV component with an EC50 value of 15.7±1.2nM. This compound has a CC50 value of 14980.0±912.0nM in cytotoxicity assay and a selective index (SI) greater than 900. The results suggested that four herbal extracts and the compound lycorine are candidates for the development of new anti-SARS-CoV drugs in the treatment of SARS.


docid: pjnfbbkl

title: COVID‐19: focus on the lungs but do not forget the gastrointestinal tract

text: The coronavirus disease 2019 (COVID‐19) caused by SARS‐CoV‐2 was declared in the last weeks as the global pandemics. Currently affecting more than 3,000,000 individuals worldwide, COVID‐19 is most commonly associated with symptoms caused by the acute respiratory distress syndrome (ARDS). As the number of infected individuals increases, we are learning that not only lungs, but also other organs can be affected by the virus. The gastrointestinal symptoms, like for example diarrhoea, vomiting, nausea, or abdominal pain are frequent in patients with COVID‐19. Moreover, alimentary tract symptoms may precede the respiratory presentation of SARS‐CoV‐2 infection. This can lead to delayed diagnosis and inappropriate management of infected patients. In addition, SARS‐CoV‐2 nucleic acid can be detected in faeces of infected patients and rectal swabs are even reported to remain positive for a longer period of time than nasopharyngeal swabs. Here, we aim to provide an update on the gastrointestinal involvement of COVID‐19 presenting the symptoms that can be encountered in infected patients. We address the role of ACE2, as a functional receptor for SARS‐CoV‐2, which also was found in the gastrointestinal tract. Finally, we briefly discuss faecal shedding of SARS‐CoV‐2 and its potential role in the pathogenesis of the disease.


title: The housefly, Musca domestica, as a possible mechanical vector of Newcastle disease virus in the laboratory and field

text: Newcastle disease (Paramyxoviridae) is a highly infectious virus shed in the faeces of infected birds. Non‐biting Muscid flies characteristically visit manure and decaying organic material to feed and oviposit, and may contribute to disease transmission. The housefly, Musca domestica (Linnaeus, 1758) (Diptera: Muscidae), has been implicated as a mechanical vector of numerous pathogens. In this study 2000 aerial net‐captured houseflies were examined for their ability to harbour Newcastle disease virus (NDV). In an adjacent study, laboratory‐reared flies were experimentally exposed to NDV La Sota strain. The virus was detected in the dissected gastrointestinal tract of laboratory‐exposed flies for up to 72 h post‐exposure, whereas the untreated control flies were negative.


title: The Taking of the Cytoskeleton One Two Three: How Viruses Utilize the Cytoskeleton During Egress

text: The final assembly of nonlytic envelope viruses requires the coordinated transport of either subviral particles or fully formed virions to the plasma membrane for release from the cell. Recent research has delved into the mechanisms viruses employ to hijack the host cell’s cytoskeletal system for active transport to the site of final assembly and release. This review will look at recent findings that relate to the transport of virions to the cell periphery and out of the cell.


title: Transmissible gastroenteritis virus targets Paneth cells to inhibit the self-renewal and differentiation of Lgr5 intestinal stem cells via Notch signaling

text: Infection with transmissible gastroenteritis virus (TGEV) has been associated with villous atrophy within 48 h, which seriously disrupts intestinal homeostasis. However, the underlying mechanisms remain elusive. In this study, we found that TGEV infection severely disrupted intestinal homeostasis via inhibition of self-renewal and differentiation in Lgr5 intestinal stem cells (ISCs). Profoundly, TGEV-encoded NSP10/NSP16 protein complex-mediated the inactivation of Notch signaling provided a mechanistic explanation for this phenomenon. Initial invasions by TGEV-targeted Paneth cells through aminopeptidase N (APN) receptor, then inducing mitochondrial damage and ROS generation in them, ultimately causing Paneth cell decrease and loss of Notch factors (DII4 and Hes5), which are essential for Lgr5 ISCs self-renewal and differentiation. Interestingly, loss of Notch signaling induced goblet cells differentiation at the cost of absorptive enterocytes and promoted mucins secretion, which accelerated TGEV replication. Therefore, the more differentiation of goblet cells, the greater TGEV infection in jejunum. These results provide a detailed mechanistic pathway by which villous atrophy sharply occurs in TGEV-infected jejunum within 48 h. Thus, the pathogenesis of TGEV can be described as a “bottom up scenario”, which is contrary to the traditional “top down” hypothesis. Together, our findings provide a potential link between diarrheal virus infection and crypt cells response that regulates Paneth cells function and Lgr5 ISCs fate and could be exploited for therapeutic application.


title: Gut microbiota of the very-low-birth-weight infant

text: The microbiome, of which the bacterial component alone (microbiota), is estimated to include 10 times more cells than human cells of the body, blooms immediately after birth and evolves in composition and complexity throughout childhood. The gut microbiome has a profound impact on gastrointestinal tract development, maintenance of mucosal surface integrity, and contributes to the nutritional status of the host and thus plays a pivotal role in health and disease. New technologies have enabled the detailed characterization of normal microbial symbionts and dysbiosis–disease associations. This review summarizes the stepwise establishment of the intestinal microbiota, influential environmental factors, and how this may be perturbed in preterm very-low-birth-weight infants. The contribution of the microbiota to provision of energy and nutrients for intestinal development and the nutritional status of the host are reviewed. In addition, the crucial role of the gut microbiota in maintaining mucosal integrity is explored along with how its breakdown can lead to sepsis, necrotizing enterocolitis, and systemic inflammatory response syndrome. Finally, the role of enteral feeding type (human milk, formula, and nutrient fortification) in mediating these processes is discussed, and guidance is provided for nutritional strategies to promote health in these fragile infants. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/pr.2014.162) contains supplementary material, which is available to authorized users.


title: Complication of Late Presenting STEMI due to Avoidance of Medical Care during COVID-19 Pandemic

text: Abstract Patients are avoiding hospitals for fear of contracting SARS-CoV-2. We are witnessing a reemergence of rare complications of myocardial infarctions (MI) due to delayed revascularization. Herein, we describe a case of hemorrhagic pericarditis from thrombolytics administered to a patient with late presenting MI.


title: Dual RNA-seq reveals viral infections in asthmatic children without respiratory illness which are associated with changes in the airway transcriptome

text: BACKGROUND: Respiratory illness caused by viral infection is associated with the development and exacerbation of childhood asthma. Little is known about the effects of respiratory viral infections in the absence of illness. Using quantitative PCR (qPCR) for common respiratory viruses and for two genes known to be highly upregulated in viral infections (CCL8/CXCL11), we screened 92 asthmatic and 69 healthy children without illness for respiratory virus infections. RESULTS: We found 21 viral qPCR-positive and 2 suspected virus-infected subjects with high expression of CCL8/CXCL11. We applied a dual RNA-seq workflow to these subjects, together with 25 viral qPCR-negative subjects, to compare qPCR with sequencing-based virus detection and to generate the airway transcriptome for analysis. RNA-seq virus detection achieved 86% sensitivity when compared to qPCR-based screening. We detected additional respiratory viruses in the two CCL8/CXCL11-high subjects and in two of the qPCR-negative subjects. Viral read counts varied widely and were used to stratify subjects into Virus-High and Virus-Low groups. Examination of the host airway transcriptome found that the Virus-High group was characterized by immune cell airway infiltration, downregulation of cilia genes, and dampening of type 2 inflammation. Even the Virus-Low group was differentiated from the No-Virus group by 100 genes, some involved in eIF2 signaling. CONCLUSIONS: Respiratory virus infection without illness is not innocuous but may determine the airway function of these subjects by driving immune cell airway infiltration, cellular remodeling, and alteration of asthmogenic gene expression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-1140-8) contains supplementary material, which is available to authorized users.


title: Drug targets for COVID-19 therapeutics: Ongoing global efforts

text: The current global pandemic COVID-19 caused by the SARS-CoV-2 virus has already inflicted insurmountable damage both to the human lives and global economy. There is an immediate need for identification of effective drugs to contain the disastrous virus outbreak. Global efforts are already underway at a war footing to identify the best drug combination to address the disease. In this review, an attempt has been made to understand the SARS-CoV-2 life cycle, and based on this information potential druggable targets against SARS-CoV-2 are summarized. Also, the strategies for ongoing and future drug discovery against the SARS-CoV-2 virus are outlined. Given the urgency to find a definitive cure, ongoing drug repurposing efforts being carried out by various organizations are also described. The unprecedented crisis requires extraordinary efforts from the scientific community to effectively address the issue and prevent further loss of human lives and health.


title: Personal protective practices and pharmacy services delivery by community pharmacists during COVID-19 pandemic: Results from a national survey

text: INTRODUCTION: Coronavirus disease (COVID19) has adversely affected the delivery of various health services. Little is known about the impact of COVID19 on pharmacy services across the United Kingdom (UK). We surveyed community pharmacists across the UK to understand their protective practices, professional and general well-being, and the delivery of pharmacy services during the COVID19 pandemic. METHODS: Community pharmacists were invited to participate in a cross-sectional survey via the nationwide weekly newsletter of Pharmaceutical Services Negotiating Committee and the local pharmaceutical committees during the second week of May 2020. The survey remained open for 4 weeks. RESULTS: A total of 206 pharmacists responded to the survey with representations from England, Northern Ireland, Scotland, and Wales. The majority of pharmacists (>75% or above) reported an increase in customer traffic to their pharmacy and were asking relevant questions from patients with flu-like symptoms before signposting them to the appropriate care. Most pharmacists (>85%) were maintaining a safe distance of 2 m from customers and 72% were wearing an N95 protective mask and 28% were using protective gloves and apron in addition to safe distancing and protective masks. Ninety-nine percent of pharmacists reported drug shortages with 38% and 26% reported significant drug shortages and critical drug shortages causing disruptions beyond over the counter medicines. Eighty-nine percent pharmacists reported inappropriate behaviour from patients or carers with 31% and 16% reported it to be a regular or frequent problem, respectively. Fifty-three% of pharmacists were willing to offer their assistance for mass testing of COVID19 antibodies if adequate training and reimbursement are provided. CONCLUSION: Community pharmacists in the UK are facing considerable challenges in terms of personal protection and the delivery of pharmacy services. Inappropriate behaviour from patients and carers towards community pharmacists require urgent attention to ensure a safe working place for all community pharmacists.


title: Chronic infections can shape epidemic exposure: Pathogen co-occurrence networks in the Serengeti lions

text: Pathogens are embedded in a complex network of microparasites that can collectively or individually alter disease dynamics and outcomes. Chronic pathogens, for example, can either facilitate or compete with subsequent pathogens thereby exacerbating morbidity and mortality. Pathogen interactions are ubiquitous in nature, but poorly understood, particularly in wild populations. We report here on ten years of serological and molecular data in African lions, leveraging comprehensive demographic and behavioral data to utilize pathogen networks to test if chronic infections shape infection by acute pathogens. We combine network and community ecology approaches to assess broad network structure and characterize associations between pathogens across spatial and temporal scales. We found significant non-random structure in the lion-pathogen co-occurrence network and identified potential facilitative and competitive interactions between acute and chronic pathogens. Our results provide a novel insight for untangling the complex associations underlying pathogen co-occurrence networks.


title: Novel Approach for Isolation and Identification of Porcine Epidemic Diarrhea Virus (PEDV) Strain NJ Using Porcine Intestinal Epithelial Cells

text: Porcine epidemic diarrhea virus (PEDV), which is the causative agent of porcine epidemic diarrhea in China and other countries, is responsible for serious economic losses in the pork industry. Inactivated PEDV vaccine plays a key role in controlling the prevalence of PEDV. However, consistently low viral titers are obtained during the propagation of PEDV in vitro; this represents a challenge to molecular analyses of the virus and vaccine development. In this study, we successfully isolated a PEDV isolate (strain NJ) from clinical samples collected during a recent outbreak of diarrhea in piglets in China, using porcine intestinal epithelial cells (IEC). We found that the isolate was better adapted to growth in IECs than in Vero cells, and the titer of the IEC cultures was 10(4.5) TCID(50)/0.1 mL at passage 45. Mutations in the S protein increased with the viral passage and the mutations tended towards attenuation. Viral challenge showed that the survival of IEC-adapted cultures was higher at the 45th passage than at the 5th passage. The use of IECs to isolate and propagate PEDV provides an effective approach for laboratory-based diagnosis of PEDV, as well as studies of the epidemiological characteristics and molecular biology of this virus.


title: A Marketing Approach to a Psychological Problem: Problematic Smartphone Use on Adolescents

text: Background: Smartphones have become an indispensable part of the daily lives of adolescents in the 21st century, which is characterized by a highly digitized modern world. Besides their many advantages, smartphones might pave the way to compulsive usage and addictive experiences. To remedy this problem, this study proposes an authentic approach which integrates consumer behavior theories and techniques such as unhook and gamification. An education program has been designed based on these approaches to decrease the problematic smartphone use. Method: The participants of the education program consisted of 305 students (48.2% girls and 51.8% boys) with a mean age of 14.57 (SD = 0.74). The Demographic Form and Smartphone Addiction Scale for Adolescents (SASA) were conducted before the education program and three weeks after the education. Results: The results of the paired sample t-test analysis before and after the education program revealed that the SASA total scores decreased significantly (p < 0.01). There are significant differences in terms of gender, mothers’ education and class levels. Conclusion: This research emphasizes the role of an interdisciplinary approach to the addiction problem. The content used in the education program includes strategies that originally aimed at increasing consumption. The effectiveness of the program can be enhanced further in the future along with self-regulatory additions.


title: Similarities between COVID-19 and anti-MDA5 syndrome: what can we learn for better care?

text: Since the end of 2019, the coronavirus disease 2019 (COVID-19) pandemic has struck worldwide, leading to more than 7 million cases by June 2020, with an approximately 5.5% mortality rate, mainly due to acute respiratory distress syndrome (ARDS) [1].


Clinical characteristics of dermatologic manifestations of COVID‐19 infection: case series of 15 patients, review of literature, and proposed etiological classification


title: Panel 7 – Pathogenesis of otitis media – a review of the literature between 2015 and 2019

text: Abstract Objective To perform a comprehensive review of the literature from July 2015 to June 2019 on the pathogenesis of otitis media. Bacteria, viruses and the role of the microbiome as well as the host response are discussed. Directions for future research are also suggested. Data sources PubMed database of the National Library of Medicine. Review methods PubMed was searched for any papers pertaining to OM pathogenesis between July 2015 and June 2019. If in English, abstracts were assessed individually for their relevance and included in the report. Members of the panel drafted the report based on these searches and on new data presented at the 20th International Symposium on Recent Advances in Otitis Media. Conclusions The main themes that arose in OM pathogenesis were around the need for symptomatic viral infections to develop disease. Different populations potentially having different mechanisms of pathogenesis. Novel bacterial otopathogens are emerging and need to be monitored. Animal models need to continue to be developed and used to understand disease pathogenesis. Implications for Practice The findings in the pathogenesis panel have several implications for both research and clinical practice. The most urgent areas appear to be to continue monitoring the emergence of novel otopathogens, and the need to develop prevention and preventative therapies that do not rely on antibiotics and protect against the development of the initial OM episode.


Sars-CoV-2: les anticorps recueillis au POC


title: Towards evidence-based, GIS-driven national spatial health information infrastructure and surveillance services in the United Kingdom

text: The term "Geographic Information Systems" (GIS) has been added to MeSH in 2003, a step reflecting the importance and growing use of GIS in health and healthcare research and practices. GIS have much more to offer than the obvious digital cartography (map) functions. From a community health perspective, GIS could potentially act as powerful evidence-based practice tools for early problem detection and solving. When properly used, GIS can: inform and educate (professionals and the public); empower decision-making at all levels; help in planning and tweaking clinically and cost-effective actions, in predicting outcomes before making any financial commitments and ascribing priorities in a climate of finite resources; change practices; and continually monitor and analyse changes, as well as sentinel events. Yet despite all these potentials for GIS, they remain under-utilised in the UK National Health Service (NHS). This paper has the following objectives: (1) to illustrate with practical, real-world scenarios and examples from the literature the different GIS methods and uses to improve community health and healthcare practices, e.g., for improving hospital bed availability, in community health and bioterrorism surveillance services, and in the latest SARS outbreak; (2) to discuss challenges and problems currently hindering the wide-scale adoption of GIS across the NHS; and (3) to identify the most important requirements and ingredients for addressing these challenges, and realising GIS potential within the NHS, guided by related initiatives worldwide. The ultimate goal is to illuminate the road towards implementing a comprehensive national, multi-agency spatio-temporal health information infrastructure functioning proactively in real time. The concepts and principles presented in this paper can be also applied in other countries, and on regional (e.g., European Union) and global levels.


TGA advises of potential taste disturbance with Andrographis paniculata


Medical reviews. Coronaviruses.


title: Outbreak of porcine epidemic diarrhoea virus (PEDV) in Abruzzi region, central‐Italy

text: Here we report and characterize a porcine epidemic diarrhea (PED) outbreak which occurred in a swine fattening farm in the province of Teramo, Abruzzi region (central Italy), in January 2016. PED virus (PEDV) identification was determined by real‐time RT‐PCR performed on RNAs purified from fecal samples collected from two symptomatic pigs. Whole genome sequence (PEDV 1842/2016) was also obtained by next generation sequencing straight from RNA purified from one fecal sample. Genome comparison with extant global PEDV strains revealed a high nucleotide identity with recently reported European and American S‐INDEL PEDVs. Efficient sequencing, share of genomic data combined with the implementation of epidemiological tools would be the ideal approach for study and analysis of transboundary infectious diseases as PED.


title: Variability analysis and inter-genotype comparison of human respiratory syncytial virus small hydrophobic gene

text: BACKGROUND: Small hydrophobic (SH) gene is one of the mostly diverse genomic regions of human respiratory syncytial virus (HRSV). Its coding region constitutes less than 50% of the complete gene length, enabling SH gene to be highly variable and the SH protein highly conserved. In standard HRSV molecular epidemiology studies, solely sequences of the second hypervariable region of the glycoprotein gene (HVR2) are analyzed. To what extent do the strains identical in HVR2 differ elsewhere in genomes is rarely investigated. Our goal was to investigate whether diversity and inter-genotype differences observed for HVR2 are also present in the SH gene. METHODS: We sequenced 198 clinical samples collected within a limited area and time frame. In this HRSV collection, rapid and significant changes in HVR2 occurred. RESULTS: Over 20% of strains from this pool (containing HRSV genotypes NA1, ON1, GA5, BA9 and BA10) would be incorrectly assumed to be identical to another strain if only the HVR2 region was analysed. The majority of differences found in SH gene were located in the 5′ untranslated region (UTR). Seven indels were detected, one was genotype GA5 specific. An in-frame deletion of 9 nucleotides (coding for amino acids 49–51) was observed in one of group A strains. Fifteen different SH protein sequences were detected; 68% of strains possessed the consensus sequence and most of others differed from the consensus in only one amino acid (only 4 strains differed in 2 amino acids). The majority of differing amino acids in group A viruses had the same identity as the corresponding amino acids in group B strains. When analysis was restricted to strains with identical HVR2 nucleotide sequences and differing SH protein sequences, 75% of differences observed in the SH ectodomain were located within region coding for amino acids 49–51. CONCLUSIONS: Basing HRSV molecular epidemiology studies solely on HVR2 largely underestimates the complexity of circulating virus populations. In strain identification, broadening of the genomic target sequence to SH gene would provide a more comprehensive insight into viral pool versatility and its evolutionary processes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1020-9) contains supplementary material, which is available to authorized users.


The Renin-Angiotensin-Aldosterone System in Coronavirus Infection – current considerations during the pandemic


title: We survived this! What managers could learn from SMEs who successfully navigated the Greek economic crisis

text: Abstract Small and medium size enterprises in both business to business and consumer markets are particularly vulnerable to economic downturns. Concentrating on the Greek economic crisis, one of the toughest and most prolonged on a global scale, the present research sheds light on both anthropocentric and business-centric factors that helped SMEs survive, therefore, providing a valuable survival manual. Per findings of two studies performed under the given economically intense conditions, it is evidenced that the right answer to survival rests upon: (a) the entrepreneurs' personality traits and skills that affect the market and entrepreneurial orientations of SMEs, (b) the adoption of such orientations that keep impacting the firms' performance, and finally (c) the implementation of strategy relevant to reaching higher quality standards for products and services, combined with tactics relevant to downsizing, marketing actions, extroversion, and financial management.


title: Chapter 14 Gastrointestinal Function

text: Publisher Summary This chapter describes the normal biochemical processes of intestinal secretion, digestion, and absorption. The digestive system is composed of the gastrointestinal (GI) tract, or the alimentary canal, salivary glands, the liver, and the exocrine pancreas. The principal functions of the gastrointestinal tract are to digest and absorb ingested nutrients, and to excrete waste products of digestion. Most nutrients are ingested in a form that is either too complex for absorption or insoluble, and therefore, indigestible or incapable of being digested. Within the GI tract, much of these substances are solubilized and further degraded enzymatically to simple molecules, sufficiently small in size, and in a form that permits absorption across the mucosal epithelium. This chapter explains in detail the mechanisms of salivary secretions, compositions of saliva, and the functions of saliva. The chapter also elaborates properties of bile as well as the synthesis of bile acids. The chapter explores the pathogenesis of the important gastrointestinal diseases of domestic animals, and the biochemical basis for their diagnosis and treatment. The chapter concludes with a discussion on disturbances of gastrointestinal function such as vomition, acute diarrheas, malabsorption, bacterial overgrowth, and ulcerative colitis.


title: Novel Insights Into Illness Progression and Risk Profiles for Mortality in Non-survivors of COVID-19

text: Background. The outbreak of COVID-19 has attracted the attention of the whole world. Our study aimed to describe illness progression and risk profiles for mortality in non-survivors. Methods. We retrospectively analyzed 155 patients with COVID-19 in Wuhan and focused on 18 non-survivors among them. Briefly, we compared the dynamic profile of biochemical and immune parameters and drew an epidemiological and clinical picture of disease progression from disease onset to death in non-survivors. The survival status of the cohort was indicated by a Kaplan–Meier curve. Results. Of the non-survivors, the median age was 73.5 years, and the proportion of males was 72.2%. Five and 13 patients were hospital-acquired and community-acquired infection of SARS-CoV-2, respectively. The interval between disease onset and diagnosis was 8.5 days (IQR, [4–11]). With the deterioration of disease, most patients experienced consecutive changes in biochemical parameters, including lymphopenia, leukocytosis, thrombocytopenia, hypoproteinemia, as well as elevated D-dimer and procalcitonin. Regarding the immune dysregulation, patients exhibited significantly decreased T lymphocytes in the peripheral blood, including CD3(+)T, CD3(+)CD4(+)Th, and CD3(+)CD8(+)Tc cells. By the end of the disease, most patients suffered from severe complications, including ARDS (17/18; 94.4%), acute cardiac injury (10/18; 55.6%), acute kidney injury (7/18; 38.9%), shock (6/18; 33.3%), gastrointestinal bleeding (1/18; 5.6%), as well as perforation of intestine (1/18; 5.6%). All patients died within 45 days after the initial hospital admission with a median survivor time of 13.5 days (IQR, 8–17). Conclusions. Our data show that patients experienced consecutive changes in biochemical and immune parameters with the deterioration of the disease, indicating the necessity of early intervention.


title: Real-time diagnosis of reactive oxygen species (ROS) in fresh sputum by electrochemical tracing; correlation between COVID-19 and viral-induced ROS in lung/respiratory epithelium during this pandemic

text: COVID-19 is the shocking viral pandemics of this year which affected the health, economy, communications, and all aspects of social activities all over the world. Early diagnosis of this viral disease is very important since it can prevent lots of mortalities and care consumption. The functional similarities between COVID-19 and COVID-2 in inducing acute respiratory syndrome lightened our mind to find a diagnostic mechanism based on early traces of mitochondrial ROS overproduction as lung cells’ dysfunctions induced by the virus. We designed a simple electrochemical sensor to selectively detect the intensity of ROS in the sputum sample (with a volume of less than 500 μl). Comparing the results of the sensor with clinical diagnostics of more than 140 normal and involved cases resulted in a response calibration with accuracy and sensitivity both 97%. Testing the sensor in more than 4 hospitals shed promising lights in ROS based real-time tracing of COVID-19 from the sputum sample.


title: Pulmonary function and bronchial reactivity 4 years after the first virus-induced wheezing

text: BACKGROUND: Wheezing illnesses among young children are common, and are a risk factor for asthma. However, determinants of childhood bronchial reactivity, a key feature of asthma, are largely unknown. Aim of this study was to determine how patient characteristics during the first severe virus-induced wheezing episode are associated with pulmonary function at pre-school age. METHODS: Study consisted of 76 children presenting with their first wheezing episode at the ages of 3 to 23 months. At study entry, viral etiology, rhinovirus genome load, atopic and clinical characteristics, and standardized questionnaire were analyzed. At 4-year follow-up visit, impulse oscillometry with exercise challenge was performed. RESULTS: At study entry, the mean age of the children was 12 months (SD 6.0), 57 (75%) were rhinovirus positive and 22 (30%) were sensitized. At follow-up visit four years later, the mean age of the children was 60 months (SD 7.9) and 37 (49%) were using asthma medication regularly (discontinued before testing in 25 [68%] children). Bronchial reactivity (≥35% change in mean crude values of resistance) after exercise challenge or bronchodilation was present in 9 (12%) children. Children with atopic sensitization at the time of the first wheezing episode were more often likely to develop bronchial reactivity (odds ratio 8.8, P = .03) than the children without sensitization. No other significant associations were found. CONCLUSIONS: Atopic sensitization at the time of the first severe wheezing episode is an important early risk factor for increased bronchial reactivity at pre-school age.


SARS-CoV2: should inhibitors of the renin–angiotensin system be withdrawn in patients with COVID-19?


title: Changes in some acute phase protein and immunoglobulin concentrations in cats affected by feline infectious peritonitis or exposed to feline coronavirus infection

text: Abstract The possible role of some acute phase proteins (APPs) and immunoglobulins in both the pathogenesis and diagnosis of feline infectious peritonitis (FIP) has been investigated. Serum protein electrophoresis and the concentration of haptoglobin (Hp), serum amyloid A (SAA), α1-acid glycoprotein (AGP), IgG and IgM were evaluated in cats exposed to feline coronavirus (FCoV) and in cats with FIP. The highest concentration of APPs was detected in affected cats, confirming the role of these proteins in supporting a clinical diagnosis of FIP. Repeated samplings from both FIP affected and FCoV-exposed cats showed that when FIP appeared in the group, all the cats had increased APP levels. This increase persisted only in cats that developed FIP (in spite of a decrease in α2-globulins) but it was only transient in FCoV-exposed cats, in which a long lasting increase in α2-globulins was observed. These results suggest that changes in the electrophoretic motility of APPs or APPs other than Hp, SAA and AGP might be involved in the pathogenesis of FIP or in protecting cats from the disease.


docid: ehyuesvf

title: The temperature and regional climate effects on communitarian COVID-19 contagion in Mexico throughout phase 1

text: Abstract Due to the close relationship between the incidence of infectious diseases by epidemics and environmental conditions, this research explores the temperature, evaporation, precipitation and regional climate effects on the local transmission of coronavirus SARS-CoV-2 inside 31 states and capital of Mexico since February 29 (national onset) to March 31, 2020. Statistical analysis was conducted to explore the association between the daily local COVID-19 confirmed positive cases (LCPC) and both climate characteristics and the daily weather reported by the regional meteorological stations. In this work, the local transmission ratio (LTR) was calculated with the regional LCPC divided by the number of the effective contagion days since regional onset in each state. The results showed a negative association between temperature (mean, max and min) and climate classification with both LCPC and LTR variables. The precipitation associated positively with LCPC and LTR. The associations between the climate classification with LCPC and LTR are statistically significant. The tropical climate (mean temperature around 25.95 °C and mean precipitation around 8.74 mm) delayed the regional onset. However, the regional onset in dry climates emerged earlier as consequence of the lower temperatures and higher precipitations (20.57 °C and 20.87 mm respectively) than the observed in the tropical climate. The fastest regional onsets were observed in tempered climates in states where the lowest temperatures and lowest precipitations were registered (19.65 °C and 8.48 mm respectively). Meteorological factors influenced the trend on the regional outbreaks in Mexican's states likely by the host predisposition and susceptibility during the cold winter season. In Mexico, the climate characteristics played a crucial role on the local infection during the phase 1 being the tempered regions (as Michoacán, Jalisco, Puebla, etc.) more vulnerable than the dry (as Chihuahua, Durango or Zacatecas, etc.) or tropical areas (as Colima, Campeche, Morelos etc.).


title: MG132-mediated inhibition of the ubiquitin–proteasome pathway ameliorates cancer cachexia

text: PURPOSE: To evaluate the effect of proteasome inhibitor MG132 in cancer cachexia and to delineate the molecular mechanism underlying. METHODS: We established an experimental cancer cachexia model by subcutaneously implanting colon 26 cells into the armpits of BALB/c mice. Following administration of MG132 at various time points, body weight, food intake, gastrocnemius muscle weight, spontaneous activity and survival of tumor-bearing mice were examined along with tumor growth. Moreover, cachectic markers including glucose, triglyceride, albumin and total proteins as well as levels of the proinflammatory cytokines TNF-α and IL-6 in serum and gastrocnemius tissue were measured. Finally, mRNA and protein levels of p65, IκBα, and ubiquitin E3 ligases MuRF1 and MAFbx in gastrocnemius muscle were assessed. RESULTS: MG132 treatment significantly alleviated cancer cachexia as demonstrated by attenuated weight loss, altered carbohydrate metabolism and muscle atrophy and increased spontaneous activity and survival time of tumor-bearing mice. MG132 reduced tumor growth and the levels of TNF-α and IL-6 in serum and gastrocnemius tissue. NF-κB, MuRF1 and MAFbx were also inhibited by MG132. Unexpectedly, MG132 was more efficient when administrated during the early stages of cachexia. MG132 had no effect on food intake of tumor-bearing mice. CONCLUSION: Our results demonstrate that MG132-induced inhibition of the ubiquitin–proteasome pathway in cancer cachexia decreased the activity of NF-κB and the degradation of IκBα, and reduced the levels of TNF-α and IL-6 in serum and gastrocnemius tissue, accompanied by downregulation of MuRF1 and MAFbx. These data suggest that MG132 is a potential therapeutic and preventive agent for cancer cachexia.


title: Evaluation of a non-prime site substituent and warheads combined with a decahydroisoquinolin scaffold as a SARS 3CL protease inhibitor

text: Abstract A non-prime site substituent and warheads combined with a decahydroisoquinolin scaffold was evaluated as a novel inhibitor for severe acute respiratory syndrome (SARS) chymotrypsin-like protease (3CLpro). The decahydroisoquinolin scaffold has been demonstrated to be an effective hydrophobic center to interact with S2 site of SARS 3CLpro, but the lack of interactions at S3 to S4 site is thought to be a major reason for the moderate inhibitory activity. In this study, the effects of an additional non-prime site substituent on the scaffold as well as effects of several warheads are evaluated. For the introduction of a desired non-prime site substituent, amino functionality was introduced on the decahydroisoquinolin scaffold, and the scaffold was constructed by Pd(II) catalyzed diastereoselective ring formation. The synthesized decahydroisoquinolin inhibitors showed about 2.4 times potent inhibitory activities for SARS 3CLpro when combined with a non-prime site substituent. The present results indicated not only the expected additional interactions with the SARS 3CLpro but also the possibility of new inhibitors containing a fused-ring system as a hydrophobic scaffold and a new warhead such as thioacetal.


title: Evidence of human coroanvirus (229E), in patients with respiratory infection, Iran, 2015: the first report

text: BACKGROUND AND OBJECTIVES: Human coronaviruses (HCoVs) are one of the main causes of upper respiratory tract infections in humans. While more often responsible for mild illness, they have been associated with illnesses that require hospitalization. MATERIALS AND METHODS: 270 Samples from patients hospitalized with the respiratory infection during the autumn season of 2015 were evaluated for the presence of four HCoVs (OC43, 229E, HUK1, and NL63) using an optimized SYBR green RT-PCR assay. RESULTS: Fifteen HCoV-229E positive samples were identified (5.5 % positive). 85% of positive samples were male with the range of age between 12- 75 years old. CONCLUSION: It is the first comprehensive study on determination of the role of human coronaviruses in respiratory infections in Iran. Our data provide a novel insight into the epidemiology of HCoVs in Iran. Further studies are needed and should include the isolation and molecular characterization of HCoVs in Iran.


title: Emerging coronaviruses: Genome structure, replication, and pathogenesis

text: The recent emergence of a novel coronavirus (2019‐nCoV), which is causing an outbreak of unusual viral pneumonia in patients in Wuhan, a central city in China, is another warning of the risk of CoVs posed to public health. In this minireview, we provide a brief introduction of the general features of CoVs and describe diseases caused by different CoVs in humans and animals. This review will help understand the biology and potential risk of CoVs that exist in richness in wildlife such as bats.


title: Morbillivirus Receptors and Tropism: Multiple Pathways for Infection

text: Morbilliviruses, which include measles virus (MeV), canine distemper virus, and rinderpest virus, are among the most important pathogens in their respective hosts and cause severe syndromes. Morbilliviruses are enveloped viruses with two envelope proteins, one of which is hemagglutinin (H) protein, which plays a role in binding to cellular receptors. During morbillivirus infection, the virus initially targets lymphoid cells and replicates efficiently in the lymph nodes. The principal cellular receptor for morbillivirus is signaling lymphocyte activation molecule (SLAM, also called CD150), which is exclusively expressed on immune cells. This feature reflects the strong lymphoid cell tropism and viral spread in the infected body. Morbillivirus infection, however, affects various tissues in the body, including the lung, kidney, gastrointestinal tract, vascular endothelium, and brain. Thus, other receptors for morbilliviruses in addition to SLAM might exist. Recently, nectin-4 has been identified as a novel epithelial cell receptor for MeV. The expression of nectin-4 is localized to polarized epithelial cells, and this localization supports the notion of cell tropism since MeV also grows well in the epithelial cells of the respiratory tract. Although two major receptors for lymphoid and epithelial cells in natural infection have been identified, morbillivirus can still infect many other types of cells with low infectivity, suggesting the existence of inefficient but ubiquitously expressed receptors. We have identified other molecules that are implicated in morbillivirus infection of SLAM-negative cells by alternative mechanisms. These findings indicate that morbillivirus utilizes multiple pathways for establishment of infection. These studies will advance our understanding of morbillivirus tropism and pathogenesis.


title: History and Future of Nucleic Acid Amplification Technology Blood Donor Testing

text: The introduction of blood donor screening by virus nucleic acid amplification technology (NAT) in the mid to late 1990s was driven by the so-called AIDS and hepatitis C virus (HCV) epidemic, with thousands of recipients of infected blood products and components. Plasma fractionators were the first to introduce NAT testing besides pathogen reduction procedures, to reduce the virus transmission risk through their products. To achieve a similar safety standard, NAT was then also introduced for labile blood components. German transfusion centres were the first to start in-house NAT testing of their donations in pools of up to 96 samples for HCV, hepatitis B virus (HBV), and human immunodeficiency virus-1 (HIV-1). Years later the diagnostics industry provided commercial HCV and HIV-1 and later HBV NAT tests on automated platforms. NAT tests for HIV-2, hepatitis A virus, and Parvovirus B19 followed, again driven by transfusion centres with their in-house tests. When severe acute respiratory syndrome corona virus (SARS-CoV) and West Nile Virus emerged it was the NAT that enabled the manufacturers and transfusion centres to instantly introduce sensitive and specific screening tests. Subsequent automation including sample preparation has significantly reduced the costs and complexity of the procedure and made it affordable to middle income countries as well. Currently more than 60 million donations per year are NAT tested worldwide and the remaining residual risk of virus transmission by blood components and products could be reduced to almost zero. Automation rendered possible the reduction of pool size in conjunction with increased throughput and sensitivity. Thus, antibody and antigen testing may be dispensable in the long run, particularly in the combination of NAT testing with pathogen reduction. There are new technologies on the horizon like digital droplet PCR, next-generation sequencing, lab-on-a-chip, and digital antigen assays, which are comparably sensitive. However, each of these has limitations, either in throughput, costs, automation, time to result, specificity, or the need for NAT as an integral part of the technology. Thus, NAT is still the shortest and most efficient means to the result. Donor screening NAT also contributed significantly to our knowledge on how fast viruses replicate, and on the respective diagnostic window. In conjunction with animal and patient studies, we have learned more about the minimal infectious dose and the epidemics in the donor population.


title: Effects of a porcine reproductive and respiratory syndrome virus infection on the development of the immune response against pseudorabies virus

text: Abstract The aim of this study was to investigate the effects of a porcine reproductive and respiratory syndrome virus (PRRSV) infection on the development of the immune response after pseudorabies virus (PRV) vaccination in pigs. Pigs were intranasally inoculated with the European PRRSV strain, Lelystad virus ter Huurne, and were vaccinated intramuscularly with PRV 2 weeks later (LV-PRV group). Control pigs were vaccinated with PRV only (PRV group). Eight weeks after PRV vaccination, pigs from both groups were challenged intranasally with wild-type PRV. We measured the lymphoproliferative, and the cytolytic responses to PRV of peripheral blood mononuclear cells (PBMC), isolated from blood samples. In addition, serum samples were examined for antibodies against PRV and LV. One week after PRV vaccination, PBMC proliferated abundantly to PRV in both groups. However, in the LV-PRV group the lymphoproliferative response declined after 1 week, whereas, in the PRV group, the lymphoproliferative response was high for 3 weeks and declined thereafter (P<0.05). After challenge, the lymphoproliferative response was 1 week earlier and was consistently and significantly higher in the PRV group than in the LV-PRV group. The PRV-specific killing was higher at 3 weeks after PRV vaccination and 5 weeks after PRV challenge 19±3 and 24±6%, respectively, in the PRV group, compared to 7±4 and 6±9%, respectively, in the LV-PRV group (P<0.05). However, later after vaccination and challenge the cytolytic response was identical in both groups. The antibody titre against PRV developed equally in both groups. After challenge, no PRV virus was isolated from both groups. From these results we conclude that, although PRRSV infection did cause changes in the time course of the T-lymphocyte response after PRV vaccination, PRRSV infection did not inhibit the development of vaccine-induced protection after PRV.


title: Correlation of High-Resolution CT, Symptoms, and Pulmonary Function in Patients During Recovery From Severe Acute Respiratory Syndrome

text: Study objectives: Little is known of the nature of the recovery period after severe acute respiratory syndrome (SARS) infection. We hypothesized that structural changes of the lung might correlate with symptoms and pulmonary function. To answer this question, we correlate findings of high-resolution CT (HRCT) with dyspnea scores and results of pulmonary function tests in patients during recovery from SARS. Design: Retrospective follow-up cohort study. Setting: University hospital. Patients: Nineteen patients who recovered from SARS-related hospitalization. Measurements: The study included HRCT scores (0 to 100), dyspnea scores (1 to 4), static and dynamic lung volumes, and diffusing capacity of the lung for carbon monoxide (Dlco). Results: The interval between hospital discharge and HRCT study or functional assessment was 31.2 ± 4.8 days (range, 25 to 38 days) [mean ± SD]. All patients had HRCT abnormalities and were assigned to two groups: ground-glass opacity (GGO) only (n = 7, 36.8%) and GGO with fibrosis (GGO+F) [n = 12, 63.2%]. Most patients (16 of 19, 84.2%) had no zonal predominance. HRCT scores correlated well with dyspnea scores (r = 0.78, p < 0.01) and with a variety of pulmonary functional variables, with Dlco being the most significant (r = − 0.923, p < 0.001). Compared with the GGO group, the GGO+F group showed significantly lower FEV1, FVC, total lung capacity, residual volume, and Dlco. Conclusions: HRCT findings correlate well with functional studies and clinical symptoms during recovery from SARS. Longer-term follow-up studies in a larger cohort of patients should be performed to investigate the clinical outcome of recovered SARS patients.


title: What patients “see” doctors in online fever clinics during COVID-19 in Wuhan?

text: OBJECTIVE: In December 2019, coronavirus disease 2019 (COVID-19) occurred in Wuhan, China. Online fever clinics were developed by hospitals, largely relieving the hospital’s burden. Online fever clinics could help people stay out of crowded hospitals and prevent the risk of cross infections. The objective of our study was to describe the patient characteristics of an online fever clinic and explore the most important concerns and question of online patients. MATERIALS AND METHODS: Our study extracted data from fever clinic records in medical information systems from January 24 to February 18, 2020 in a tertiary hospital in Wuhan. We described the characteristics of patients in fever clinic, then we extracted and classified questions of patient consultations through the online fever clinic dataset. RESULTS: For the 64 487 patients who attended the online fever clinic, the average age was 30.4 years, and 37 665 (58.4%) were female patients. The current state of patients from online were home without isolation (52 360 [81.2%]), home isolated (11 152 [17.29%]), and outpatient observation (975 [1.51%]). From the 594 patient questions analyzed, confirming diagnosis and seeking medical treatment account for 60.61% and 38.05%, respectively, followed by treating (25.59%), preventing (4.38%), and relieving anxiety (1.68%). DISCUSSION: Online fever clinics can effectively relieve patients’ mood of panic, and doctors can guide patients with suspected of COVID-19 to isolate and protect themselves through online fever clinic. Online fever clinics can also help to reduce the pressure of hospital fever clinics and prevent cross infection. CONCLUSIONS: This study indicated the importance of online fever clinics during the COVID-19 outbreak for prevention and control.


title: Microbiological disinfection of water and air by photocatalysis

text: Abstract This article is aimed at presenting (i) a fundamental research on the efficiency of photocatalysis in water disinfection and (ii) the efficiency of a photocatalytic prototype, developed by Buxair firm, to remove avian influenza virus in air. In water disinfection, two model strains of Escherichia coli (K12 PHL849 and K12 PHL1273) were selected and a comparison of the efficiencies of TiO2 Degussa P-25 versus TiO2 Millennium PC500 were estimated. A more important inactivation of E. coli PHL1273 was obtained on TiO2 Millennium PC500, in line with its better adherence on this solid. An experimental study was performed using a dialysis membrane to investigate the impact of the contact between the microorganisms and the photocatalyst and to determine the role of H2O2 generated in situ. In air disinfection, a total inactivation of virus A/H5N2, close to avian influenza virus A/H5N2, was obtained in a single pass in the Buxair® gas phase dynamic photoreactor using a contaminated air flow rate of 40m3/h.


docid: xwjtjopl

title: A Novel Coronavirus (COVID-19) Outbreak A Call for Action


title: Conserved aspartic acid 233 and alanine 231 are not required for poliovirus polymerase function in replicons

text: Nucleic acid polymerases have similar structures and motifs. The function of an aspartic acid (conserved in all classes of nucleic acid polymerases) in motif A remains poorly understood in RNA-dependent RNA polymerases. We mutated this residue to alanine in a poliovirus replicon. The resulting mutant could still replicate, although at a reduced level. In addition, mutation A231C (also in motif A) yielded high levels of replication. Taken together these results show that poliovirus polymerase conserved residues D233 and A231 are not essential to poliovirus replicon function.


Coronaviridae (1)


title: Passive immunization

text: Immediate protection of an animal can be achieved by passive immunization—the administration of preformed antibodies to a susceptible animal. These antibodies have historically been produced in hyperimmunized horses. The most widely employed are antitoxins directed against clostridia, such as tetanus or botulism, and snake venoms. Polyclonal antibodies are also administered to neonatal animals to protect against infections such as Rhodococcus equi in foals. Monoclonal antibodies are more specific reagents that are currently being used for the treatment of atopic dermatitis, certain cancers, and selected infectious diseases. Intravenous immunoglobulins are being used to treat autoimmune diseases.


title: Parental bonding and attitudes toward suicide among medical college students in Japan

text: BACKGROUND: Suicide is a grave public health issue that is responsible for a high mortality rate among individuals aged 15–44 years. Attitudes toward suicide among medical staff members have been associated with appropriate therapeutic responses to suicidal individuals. The aim of this study was to examine the effects of parental rearing on attitudes toward suicide among Japanese medical college students. METHODS: We examined the association between parental bonding and attitudes toward suicide in 160 medical college students in Japan. The Parental Bonding Instrument was used to assess the attitudes and behaviors of parents. The attitudes toward suicide were evaluated using the Japanese version of the Attitudes Toward Suicide questionnaire. RESULTS: The mean age of the subjects was 25.2±4.0 years old. The majority of the participants in our study agreed that anyone could commit suicide (88.8%) and that suicide is preventable (86.3%). After adjusting for age and sex, multivariate regression analysis revealed that maternal care approached a statistically significant association with the “right to suicide” attitude. Under the same conditions, maternal care was shown to be significantly associated with the “common occurrence” attitude. No other significant relationships were observed between parental bonding and attitudes toward suicide. CONCLUSION: This study suggests that a higher level of maternal care ensures that children think that suicide occurs less commonly. The promotion of best practices for suicide prevention among medical students is needed. Child rearing support might be associated with suicide prevention.


title: Lower respiratory tract viral infections: Diagnostic role of exfoliative cytology

text: Viral lower respiratory tract infections (VLRTI) remain one of the most common causes of morbidity and mortality worldwide. For many years, the diagnosis of VLRTI was based on laboratory techniques such as viral isolation in cell culture, antigen detection by direct fluorescent antibody staining, and rapid enzyme immunoassay. Radiological imaging and morphology also play an important role in diagnosing these infections. Exfoliative cytology provides a simple, rapid, inexpensive, and valuable means to diagnose and manage VLRTI. Here we review viral‐associated cytomorphological changes seen in exfoliated cells of the lower respiratory tract. Diagn. Cytopathol. 2017;45:614–620. © 2017 Wiley Periodicals, Inc.


title: ATeam technology for detecting early signs of viral cytopathic effect

text: Adenosine 5’-triphosphate (ATP), the major energy currency of the cell, is involved in many cellular processes, including the viral life cycle, and can be used as an indicator of early signs of cytopathic effect (CPE). In this study, we demonstrated that CPE can be analyzed using an FRET-based ATP probe named ATP indicator based on Epsilon subunit for Analytical Measurements (ATeam). The results revealed that as early as 3 hr, the virus infected cells showed a significantly different Venus/cyan fluorescent protein (CFP) ratio compared to the mock-infected cells. The ATeam technology is therefore useful to determine the early signs of ATP-based CPE as early as 3 hr without morphology-based CPE by light microscopy, and enables high throughput determination of the presence of microorganisms in neglected samples stored in laboratories.


title: Management of the COVID-19 epidemic by public health establishments - Analysis by the Fédération Hospitalière de France

text: Summary The objective of this article is to detail the measures taken in public institutions to cope with the COVID-19 epidemic. It details the initial strategy, organizational evolution towards "all-COVID", coordination between the various stakeholders and the strategy for maintaining continuity of care. The Quebec experience is also used as an example. Finally, an exit strategy must be anticipated at this phase of the epidemic. Face to the COVID-19 epidemic, the Fédération Hospitalière de France (French hospital federation) took prompt action as soon as the first cases were reported. The objective of this article is to detail these preparatory steps and their development in public institutions, in France and in Canada.


docid: mwnlsewg

title: Animal virus receptors

text: The term ‘receptor’ is generally accepted as the cell-surface component that participates in virus binding and facilitates subsequent viral infection. Recent advances in technology have permitted the identification of several virus receptors, increasing our understanding of the significance of this initial virus-cell and virus-host interaction. Virus binding was previously considered to involve simple recognition and attachment to a single cell surface molecule by virus attachment proteins. The classical concept of these as single entities that participate in a lock-and-key-type process has been superseded by new data indicating that binding can be a multistep process, often involving different virus-attachment proteins and more than one host-cell receptor.


title: Adventitious Agents and Smallpox Vaccine in Strategic National Stockpile

text: In keeping with current standards, we urge that old smallpox vaccines that were made in animal skin and are still a key part of our strategic national stockpile be tested for adventitious infectious agents. The advisory especially applies to viruses that have the potential for zoonotic transmission to human vaccine recipients.


title: Experimental allergic encephalomyelitis induced by the peptide encoded by exon 2 of the MBP gene, a peptide implicated in remyelination

text: Abstract The discovery of T lymphocytes reactive to the peptide encoded by exon 2 of the myelin basic protein (MBP) gene in multiple sclerosis (MS) patients has drawn attention to MBP isoforms harboring that peptide as candidate autoantigens. Previously, immunological studies in MS had almost exclusively used the more abundant 18.5 kDa isoform of MBP, which does not does not contain the exon 2 peptide. Investigations of experimental allergic encephalomyelitis (EAE) have also focussed on the 18.5 kDa MBP isoform and its peptides. Since EAE is an animal model widely used widly used to study MS, we examined the encephalitogenic potential of exon 2 peptide in the SJL/J mouse. Evidence for increased expression of exon 2-containing isoforms during remyelination in mouse CNS suggested that exon 2-sensitized T cels, with encephalitogenic capacity, might be important in the pertuation of relapsing EAE (rEAE). Our experiments have demonstrated that exon 2 peptide is inherently immunogenic in SJL mice and that EAE could be induced by the adoptive transfer of exon 2-sensitized lymphocytes. Furthermore, the disease could be accentuated by the transfer of short-term exon 2-reactive lines or by a combination of adoptive transfer and antigenic challenge with exon 2 peptide. The immunodominant epitope(s) appeared to localize to the segment bordered by amino acids 59–85.


Forgotten Emergencies During Focus on Novel Coronavirus 2019


title: Human coronavirus circulation in the United States 2014–2017

text: Abstract Background Human coronaviruses (HCoVs) -OC43, -229E, -NL63 and -HKU1 cause upper and lower respiratory tract infections. HCoVs are globally distributed and the predominant species may vary by region or year. Prior studies have shown seasonal patterns of HCoV species and annual variation in species prevalence but national circulation patterns in the US have not yet been described. Objectives To describe circulation patterns of HCoVs -OC43, -229E, -NL63 and -HKU1 in the US. Study design We reviewed real-time reverse transcription polymerase chain reaction (rRT-PCR) test results for HCoV-OC43, -229E, -NL63 and -HKU1 reported to The National Respiratory and Enteric Virus Surveillance System (NREVSS) by U.S. laboratories from July 2014–June 2017. We calculated the total number of tests and percent positive by week. For a subset of HCoV positive submissions with age and sex of the patient available, we tested for differences in age and sex across the four HCoV species using Chi Square and Kruskal Wallace tests. Results 117 laboratories reported 854,575 HCoV tests; 2.2% were positive for HCoV-OC43, 1.0% for HCoV-NL63, 0.8% for HCoV-229E, and 0.6% for HCoV-HKU1. The percentage of positive tests peaked during December – March each year. No significant differences in sex were seen across species, although a significant difference in age distribution was noted. Conclusions Common HCoVs may have annual peaks of circulation in winter months in the US, and individual HCoVs may show variable circulation from year to year. Different HCoV species may be detected more frequently in different age groups. Further years of data are needed to better understand patterns of activity for HCoVs.


title: Short fractionation radiotherapy for early prostate cancer in the time of COVID-19: long-term excellent outcomes from a multicenter Italian trial suggest a larger adoption in clinical practice

text: INTRODUCTION: To evaluate stereotactic body radiotherapy (SBRT) in low-risk Prostate Cancer patients as preferred treatment option in emergency health conditions. MATERIALS AND METHODS: From April 2013 to September 2015, 28 patients with low-risk prostate cancer were prospectively enrolled. The SBRT prescribed dose was 36.25 Gy in 5 fractions, twice a week. Primary endpoints were acute and late toxicity. Secondary endpoints were biochemical recurrence free survival (bRFS) and overall survival. RESULTS: Median follow-up was 65.5 months (range 52–81). No acute G3 or G4 toxicity was recorded. Acute G1 or G2 genitourinary (GU) toxicity occurred in 43% and acute G1–G2 gastrointestinal (GI) toxicity in 14%. Late G1 and G3 GU toxicity in 18% and 3.5%, respectively. The G3 toxicity was not directly attributable to radiotherapy. Late G1 GI toxicity occurred in 18%. 5yy bRFS was 96.5% (95% CI 82.3–99.4%). CONCLUSIONS: Stereotactic body radiotherapy for early prostate cancer reported safe toxicity profile and a good clinical outcome at the median follow-up of 5 years. It may be an useful option if radiotherapy is required in emergency medical conditions.


title: Incidence, Etiology, and Outcomes of Community-Acquired Pneumonia: A Population-Based Study

text: BACKGROUND: The microbial etiology of community-acquired pneumonia (CAP) is often unclear in clinical practice, and previous studies have produced variable results. Population-based studies examining etiology and incidence are lacking. This study examined the incidence and etiology of CAP requiring hospitalization in a population-based cohort as well as risk factors and outcomes for specific etiologies. METHODS: Consecutive admissions due to CAP in Reykjavik, Iceland were studied. Etiologic testing was performed with cultures, urine-antigen detection, and polymerase chain reaction analysis of airway samples. Outcomes were length of stay, intensive care unit admission, assisted ventilation, and mortality. RESULTS: The inclusion rate was 95%. The incidence of CAP requiring hospitalization was 20.6 cases per 10000 adults/year. A potential pathogen was detected in 52% (164 of 310) of admissions and in 74% (43 of 58) with complete sample sets. Streptococcuspneumoniae was the most common pathogen (61 of 310, 20%; incidence: 4.1/10000). Viruses were identified in 15% (47 of 310; incidence: 3.1/10000), Mycoplasmapneumoniae were identified in 12% (36 of 310; incidence: 2.4/10000), and multiple pathogens were identified in 10% (30 of 310; incidence: 2.0/10000). Recent antimicrobial therapy was associated with increased detection of M pneumoniae (P < .001), whereas a lack of recent antimicrobial therapy was associated with increased detection of S pneumoniae (P = .02). Symptoms and outcomes were similar irrespective of microbial etiology. CONCLUSIONS: Pneumococci, M pneumoniae, and viruses are the most common pathogens associated with CAP requiring hospital admission, and they all have a similar incidence that increases with age. Symptoms do not correlate with specific agents, and outcomes are similar irrespective of pathogens identified.


docid: gcmrdote

title: Nucleolar Localization of HIV-1 Rev Is Required, Yet Insufficient for Production of Infectious Viral Particles

text: Combination antiretroviral therapy fails in complete suppression of HIV-1 due to drug resistance and persistent latency. Novel therapeutic intervention requires knowledge of intracellular pathways responsible for viral replication, specifically those untargeted by antiretroviral drugs. An understudied phenomenon is the nucleolar localization of Rev phosphoprotein, which completes nucleocytoplasmic transport of unspliced/partially spliced HIV mRNA through multimerization with intronic cis-acting targets—the Rev-response element (RRE). Rev contains a nucleolar localization signal (NoLS) comprising the COOH terminus of the arginine-rich motif for accumulation within nucleoli—speculated as the interaction ground for Rev with cellular proteins mediating mRNA-independent nuclear export and splicing. Functionality of Rev nucleolar access during HIV-1 production and infection was investigated in the context of deletion and single-point mutations within Rev-NoLS. Mutations induced upon Rev-NoLS are hypothesized to inactivate the HIV-1 infectious cycle. HIV-1(HXB2) replication ceased with Rev mutations lacking nucleolar access due to loss or replacement of multiple arginine residues. Rev mutations missing single arginine residues remained strictly nucleolar in pattern and participated in proviral production, however, with reduced efficiency. Viral RNA packaging also decreased in efficiency after expression of nucleolar-localizing mutations. These results were observed during propagation of variant HIV-1(NL4-3) containing nucleolar-localizing mutations within the viral backbone (M4, M5, and M6). Lentiviral particles produced with Rev single-point mutations were transducible at extremely low frequency. Similarly, HIV-1(NL4-3) Rev-NoLS variants lost infectivity, unlike virulent WT (wild type) HIV-1(NL4-3). HIV-1(NL4-3) variants were capable of CD4(+) host entry and reverse transcription as WT HIV-1(NL4-3), but lacked ability to complete a full infectious cycle. We currently reveal that viral integration is deregulated in the presence of Rev-NoLS mutations.


title: From hidden outbreaks to epidemic emergencies: the threat associated with neglecting emerging pathogens

text: Abstract Not all infectious disease outbreaks undergo full epidemiological investigations. In certain situations, the resultant lack of knowledge has led to the development of epidemics and public health emergencies. This review will examine six emerging pathogens including their history, present status, and potential to expand to epidemics. Recommendations to improve our understanding of these hidden outbreaks and others also will be provided in the context of health systems policy.


title: Immunoglobulins in the treatment of COVID-19 infection: Proceed with caution!()

text: The COVID-19 pandemic is one of the greatest infectious challenges in recent history. Presently, few treatment options exist and the availability of effective vaccines is at least one year away. There is an urgent need to find currently available, effective therapies in the treatment of patients with COVID-19 infection. In this review, we compare and contrast the use of intravenous immunoglobulin and hyperimmune globulin in the treatment of COVID-19 infection.


title: Virus-induced modulation of lower airway diseases: Pathogenesis and pharmacologic approaches to treatment

text: Abstract Uncomplicated upper respiratory viral infections are the most common cause of days lost from work and school and exert a major economic burden. In susceptible individuals, however, common respiratory viruses, particularly human rhinoviruses, also can have a major impact on diseases that involve the lower airways, including asthma, chronic obstructive pulmonary diseases (COPD) and cystic fibrosis (CF). Respiratory virus-induced wheezing illnesses in early life are a significant risk factor for the subsequent development of asthma, and virus infections may also play a role in the development and progression of airway remodeling in asthma. It is clear that upper respiratory tract virus infections can spread to the lower airway and trigger acute attacks of asthma, COPD or CF. These exacerbations can be life-threatening, and exert an enormous burden on health care systems. In recent years we have gained new insights into the mechanisms by which respiratory viruses may induce acute exacerbations of lower airway diseases, as well as into host defense pathways that may regulate the outcomes to viral infections. In the current article we review the role of viruses in lower airway diseases, including our current understanding on pathways by which they may cause remodeling and trigger acute exacerbations. We also review the efficacy of current and emerging therapies used to treat these lower airway diseases on the outcomes due to viral infection, and discuss alternative therapeutic approaches for the management of virus-induced airway inflammation.


title: Human bocavirus and rhino-enteroviruses in childhood otitis media with effusion

text: Abstract Background Viral respiratory infections play an important role in the pathogenesis of otitis media with effusion (OME) in children. The most common human rhinoviruses (HRVs) have been detected in middle ear effusions (MEE), but there is only limited data available about the closely related human enteroviruses (HEVs). The newly discovered human bocavirus (HBoV) has not, however, been identified in MEE of OME children. Objectives The aim of our study was to determine the presence of HBoV and HRV/HEV and the rate of coinfection in a set of MEE samples collected from OME children. Study design Seventy-five MEE samples from 54 children with no acute respiratory symptoms were studied with reverse transcription polymerase chain reaction (RT-PCR) for detection of HRV/HEV and quantitative PCR for detection of HBoV. Results Twenty-six (35%) of 75 MEE samples were positive for viral nucleic acid, 22 (29%) for HEV, 10 (13%) for HRV and 2 (3%) for HBoV. There was no statistically significant difference between mucoid and serous effusions in the rate of virus detection. Forty-three percent of bilateral cases showed a contra-lateral difference in viral finding. Conclusions Our results suggest that these common respiratory viruses can be associated with OME in children. Whether these viruses are causative etiologic factors of MEE persistence or merely remnants of previous infections is not known.


title: Chapter 2: Ring-Expanded (‘Fat‘) Purines and their Nucleoside/Nucleotide Analogues as Broad-Spectrum Therapeutics

text: Publisher Summary This chapter describes a family of ring-expanded purines, informally referred to as “fat” or f-purines, as well as their nucleoside/nucleotide analogues (RENs/RENTs) that have broad applications in chemistry, biology, and medicine. Although purine itself has never been found in nature, substituted purines, such as adenine and guanine, or their respective nucleoside derivatives, adenosine and guanosine, are the most ubiquitous class of nitrogen heterocycles and play crucial roles in wide variety of functions of living beings As nucleotides (AMP,GMP), they are the building blocks of nucleic acids (RNA/DNA). They serve as energy cofactors (ATP, GTP), as part of coenzymes (NAD/FAD) in oxidation-reduction reactions, as important second messengers in many intracellular signal transduction processes (cAMP/cGMP), or as direct neurotransmitters by binding to purinergic receptors (adenosine receptors). Therefore, it is not surprising that the analogues of purines have found utility both as chemotherapeutics (antiviral, antibiotic, and anticancer agents) and pharmacodynamic entities (the regulation of myocardial oxygen consumption and cardiac blood flow). While they can act as substrates or the inhibitors of the enzymes of purine metabolism to render their chemotherapeutic action, their ability to act as agonists or antagonists of A1/A2A receptors is the basis for the modulation of pharmacodynamic property.


Low risk for SARS-CoV2 symptomatic infection and early complications in pediatric patients during the ongoing CoVID19 epidemics in Lombardy


title: Open Synthesis and the coronavirus (COVID-19) pandemic in 2020

text: • Open Science principles are vital for ensuring reproducibility, trust and legacy; • Evidence synthesis is a vital means of summarising research for decision-making; • Open Synthesis is the application of Open Science principles to evidence synthesis; • Open approaches to planning, conducting and reporting synthesis have many benefits; • We call on the evidence synthesis community to embrace Open Synthesis.


title: Direct diagnostic testing of SARS-CoV-2 without the need for prior RNA extraction.

text: The COVID-19 pandemic has resulted in an urgent global need for rapid, point-of-care diagnostic testing. Existing methods for nucleic acid amplification testing (NAAT) require an RNA extraction step prior to amplification of the viral RNA. This step necessitates the use of a centralized laboratory or complex and costly proprietary cartridges and equipment, and thereby prevents low-cost, scalable, point-of-care testing. We report the development of a highly sensitive and robust, easy-to-implement, SARS-CoV-2 test that utilizes isothermal amplification and can be run directly on viral transport media following a nasopharyngeal swab without the need for prior RNA extraction. Our assay provides visual results in 30 min with 85% sensitivity, 100% specificity, and a limit of detection (LoD) of 2.5 copies/l, and can be run using a simple heat block.


title: Serosurvey of mountain lions in southern Arizona

text: An understanding of the prevalence of diseases in free‐ranging populations of felids is limited, and there is even less known about the overall health and diseases of wild felids that inhabit or utilize urban areas. We collected serum samples from 9 radiocollared mountain lions (Puma concolor) in the mountains surrounding Tucson, Arizona, USA, from August 2005 to August 2008. We tested serum samples for evidence of exposure to 10 feline viruses: Feline Calicivirus (FCV), Feline Herpesvirus, Feline Enteric Coronavirus, Feline Syncytial Virus–Feline Foamy Virus, Feline Infectious Peritonitis, Feline Immunodeficiency Virus, Feline Panleukopenia Virus (FPLV), Feline Leukemia Virus, Canine Distemper Virus (CDV), and Toxoplasma gondii. The highest prevalences of exposure were: T. gondii (8/9), FPLV (7/9), and FCV (6/9). One male was seropositive for CDV, T. gondii, and FPLV. Mountain lions inhabiting smaller fragmented landscapes and urban areas have more contact with other felids and domesticated animals. Frequent contact among mountain lions, other felids, and domesticated animals can lead to higher risk of exposure and facilitate the spread of the disease from animal to animal. © 2012 The Wildlife Society.


docid: jhahmprm

title: Host with the most: Targeting host cells instead of pathogens to fight infectious disease


title: Virome diversity analysis reveals novel enteroviruses and a human picobirnavirus in stool samples from African green monkeys with diarrhea

text: It is important to identify viruses in animals because most infectious diseases in humans are caused by viruses of zoonotic origin. African green monkey is a widely used non-human primate model in biomedical investigations. In this study, total RNAs were extracted from stool samples of 10 African green monkeys with diarrhea. High-throughput sequencing was used to characterize viromes. PCR and Sanger sequencing were used to determine the full genome sequences. Great viral diversity was observed. The dominant viruses were enteroviruses and picobirnaviruses. Six enterovirus genomes and a picobirnavirus RNA-dependent RNA polymerase sequence were characterized. Five enteroviruses belonged to two putative new genotypes of species Enterovirus J. One enterovirus belonged to EV-A92. The picobirnavirus RNA-dependent RNA polymerase sequence had the highest nucleotide similarity (93.48%) with human picobirnavirus isolate GPBV6C2. The present study helped to identify the potential zoonotic viruses in African green monkeys. Further investigations are required to elucidate their pathogenic roles in animals and humans.


title: A Proposed Strategy for Management of Immunosuppression in Heart Transplant Patients with COVID‐19

text: There is limited experience in management of orthotopic heart transplant (OHT) patients with COVID‐19. In this study, we present our initial experience using a standardized management algorithm. Data collection was performed on OHT patients with COVID‐19 after March 10, 2020 (declaration of state‐of‐emergency in Massachusetts). Among the 358 OHT patients currently followed at our program, 5 patients (1.4%) tested positive for COVID‐19 (median age 50 years [IQR, 49‐58], duration post‐OHT 21 years [IQR, 6‐25], and 4 of 5 (80%) were men). Among the 5 OHT patients, 2 of 5 (20%) had mild disease, and had no change in baseline immunosuppression therapy. Two of 5 (20%) had moderate disease, and received remdesivir as part of a clinical trial, and reduced immunosuppression therapy. One patient (20%) died prior to presenting to the hospital, consistent with 20% case fatality rate.


title: Influenza vaccine coverage rates and perceptions on vaccination in South Korea

text: Summary Objective This survey was performed to assess the level of influenza vaccine coverage, to understand the driving forces and barriers to vaccination and determine vaccination interventions for the following year in Korean population. Methods A national sample of 1720 community dwelling adults of age 18 and older were surveyed by individual visits during April 2005. Demographics, state of influenza vaccination, reasons for vaccination or non-vaccination and perceptions on vaccinations were asked by questionnaire. Results Influenza vaccination coverage in general population and high risk group was 34.3% and 61.3%, respectively. Predictors for vaccination were ≥65 of age, performance of regular exercise, vaccination in the previous season, experience of influenza-like illness, belief that vaccine can prevent common cold and opinion that vaccine must be taken annually. The most common reason for vaccination for both whole population and high risk groups was to prevent both influenza and common cold, while the most common reason for non-vaccination was the thought that he/she was healthy enough not to be in need for vaccination. Having more information on influenza and vaccination as well as doctor's recommendation for vaccination appeared to be the most important modus operandi to encourage influenza vaccination among non-vaccinees. Conclusions Doctor's recommendation was the most important factor in encouraging people to be vaccinated against influenza. Doctors should be geared up with precise information and actively encourage high risk population in order to increase vaccination coverage.


docid: cbwnenjh

title: Prolonged Confusional state as first manifestation of COVID‐19

text: A 77 year old gentleman, normally fit and well, was admitted with acute confusion. On admission GCS was 14/15, vital signs were within the normal limits and bilateral crepitation at the lung base. Head CT scan normal. CXR showed some air space opacification. Investigations revealed hyponatraemia, raised CRP and positive for COVID‐19. Treated with antibiotics and intravenous saline, sodium returned to normal. Delirium remained unchanged four weeks post incidence. Neurological manifestations were documented in patients with COVID‐19, however no report has shown delirium as a primary manifestation. This case illustrates acute confusion may be the only presenting symptom of COVID‐19 without overt lung disease.


title: Maintaining Treatment Integrity in the Face of Crisis: A Treatment Selection Model for Transitioning Direct ABA Services to Telehealth

text: With health care funders’ increasing approval of telehealth service as an emergency measure to provide continuity of care during the COVID-19 crisis, practicing behavior analysts have an unprecedented opportunity to demonstrate that essential, medically necessary behavior-analytic services can be provided via telehealth in a manner that maintains treatment integrity and produces meaningful client outcomes. This telehealth treatment selection guide was designed to assist practicing behavior analysts in determining an appropriate protocol for the delivery of 1:1 telehealth service (i.e., a behavior technician providing instruction directly to a client, with or without the assistance of the client’s caregiver, through videoconferencing). This tool aims to help behavior analysts make thoughtful clinical decisions to maintain continuity of care for the vulnerable population with autism spectrum disorders, while adhering to safety measures that provide protection to society.


title: Tocilizumab in patients with severe COVID-19: a retrospective cohort study

text: BACKGROUND: No therapy is approved for COVID-19 pneumonia. The aim of this study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment. METHODS: This retrospective, observational cohort study included adults (≥18 years) with severe COVID-19 pneumonia who were admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between Feb 21 and April 30, 2020. All patients were treated with the standard of care (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab. Tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total), when the intravenous formulation was unavailable. The primary endpoint was a composite of invasive mechanical ventilation or death. Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for sex, age, recruiting centre, duration of symptoms, and baseline Sequential Organ Failure Assessment (SOFA) score. FINDINGS: Of 1351 patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in the study. 57 (16%) of 365 patients in the standard care group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (p=0·41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91 patients treated subcutaneously). 73 (20%) patients in the standard care group died, compared with 13 (7%; p<0·0001) patients treated with tocilizumab (six [7%] treated intravenously and seven [8%] treated subcutaneously). After adjustment for sex, age, recruiting centre, duration of symptoms, and SOFA score, tocilizumab treatment was associated with a reduced risk of invasive mechanical ventilation or death (adjusted hazard ratio 0·61, 95% CI 0·40–0·92; p=0·020). 24 (13%) of 179 patients treated with tocilizumab were diagnosed with new infections, versus 14 (4%) of 365 patients treated with standard of care alone (p<0·0001). INTERPRETATION: Treatment with tocilizumab, whether administered intravenously or subcutaneously, might reduce the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia. FUNDING: None.


Definitive Airway Management of Patients with a King Laryngeal Tube(™) in Place in the COVID-19 Pandemic


The chain of communication in health science: from researcher to health worker through open access


title: MERS-CoV infection among healthcare workers and risk factors for death: Retrospective analysis of all laboratory-confirmed cases reported to WHO from 2012 to 2 June 2018

text: Abstract Background Approximately half of the reported laboratory-confirmed infections of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in healthcare settings, and healthcare workers constitute over one third of all secondary infections. This study aimed to describe secondary cases of MERS-CoV infection among healthcare workers and to identify risk factors for death. Methods A retrospective analysis was conducted on epidemiological data of laboratory-confirmed MERS-CoV cases reported to the World Health Organization from September 2012 to 2 June 2018. We compared all secondary cases among healthcare workers with secondary cases among non-healthcare workers. Multivariable logistic regression identified risk factors for death. Results Of the 2223 laboratory-confirmed MERS-CoV cases reported to WHO, 415 were healthcare workers and 1783 were non-healthcare workers. Compared with non-healthcare workers cases, healthcare workers cases were younger (P < 0.001), more likely to be female (P < 0.001), non-nationals (P < 0.001) and asymptomatic (P < 0.001), and have fewer comorbidities (P < 0.001) and higher rates of survival (P < 0.001). Year of infection (2013–2018) and having no comorbidities were independent protective factors against death among secondary healthcare workers cases. Conclusion Being able to protect healthcare workers from high threat respiratory pathogens, such as MERS-CoV is important for being able to reduce secondary transmission of MERS-CoV in healthcare-associated outbreaks. By extension, reducing infection in healthcare workers improves continuity of care for all patients within healthcare facilities.


title: Asymmetric effects of investor sentiment on industry stock returns: Panel data evidence

text: Abstract This article employs a state-of-the-art panel threshold model by allowing for regime intercepts, in order to shed new light on the asymmetric/nonlinear effects of local and global sentiments on expected industry stock returns among 11 Asian countries during the period from 1996 to 2010. Empirical evidence demonstrates that once the regime intercept is included, the asymmetric effects of global sentiment on oil & gas, financials, and health care industry returns become less under optimism, as compared with under pessimism. More critically, the positive (negative) impact of global sentiment above (under) the threshold turns significant, indicating that global optimism leads industry returns to be overvalued, while pessimism leads them to be undervalued. For local market sentiment, our results support that higher local sentiment enhances the returns of basic materials, telecommunications, and utilities industries. The empirical results confirm that the nexus of industry returns and investor sentiments is subject to change between different sentimental intervals.


title: Post-exposure prophylaxis or pre-emptive therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): study protocol for a pragmatic randomized-controlled trial

text: BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 causing the coronavirus disease (COVID-19) pandemic. Currently, there is a lack of evidence-based therapies to prevent COVID-19 following exposure to the virus, or to prevent worsening of symptoms following confirmed infection. We describe the design of a clinical trial of hydroxychloroquine for post-exposure prophylaxis (PEP) and pre-emptive therapy (PET) for COVID-19. METHODS: We will conduct two nested multicentre international double-blind randomized placebo-controlled clinical trials of hydroxychloroquine for: 1) PEP of asymptomatic household contacts or healthcare workers exposed to COVID-19 within the past four days, and 2) PET for symptomatic outpatients with COVID-19 showing symptoms for less than four days. We will recruit 1,500 patients each for the PEP and PET trials. Participants will be randomized 1:1 to receive five days of hydroxychloroquine or placebo. The primary PEP trial outcome will be the incidence of symptomatic COVID-19. The primary PET trial outcome will be an ordinal scale of disease severity (not hospitalized, hospitalized without intensive care, hospitalization with intensive care, or death). Participant screening, informed consent, and follow-up will be exclusively internet-based with appropriate regulatory and research ethics board approvals in Canada and the United States. DISCUSSION: These complementary randomized-controlled trials are innovatively designed and adequately powered to rapidly answer urgent questions regarding the effectiveness of hydroxychloroquine to reduce virus transmission and disease severity of COVID-19 during a pandemic. In-person participant follow-up will not be conducted to facilitate social distancing strategies and reduce risks of exposure to study personnel. Innovative trial approaches are needed to urgently assess therapeutic options to mitigate the global impact of this pandemic. TRIALS REGISTRATION: clinicaltrials.gov (NCT04308668); registered 16 March, 2020.