title: Social network theory in the behavioural sciences: potential applications

text: Social network theory has made major contributions to our understanding of human social organisation but has found relatively little application in the field of animal behaviour. In this review, we identify several broad research areas where the networks approach could greatly enhance our understanding of social patterns and processes in animals. The network theory provides a quantitative framework that can be used to characterise social structure both at the level of the individual and the population. These novel quantitative variables may provide a new tool in addressing key questions in behavioural ecology particularly in relation to the evolution of social organisation and the impact of social structure on evolutionary processes. For example, network measures could be used to compare social networks of different species or populations making full use of the comparative approach. However, the networks approach can in principle go beyond identifying structural patterns and also can help with the understanding of processes within animal populations such as disease transmission and information transfer. Finally, understanding the pattern of interactions in the network (i.e. who is connected to whom) can also shed some light on the evolution of behavioural strategies.


title: Design, synthesis, antiviral and cytotoxic evaluation of novel acyclic phosphonate nucleotide analogues with a 5,6-dihydro-1H-[1,2,3]triazolo[4,5-d]pyridazine-4,7-dione system

text: ABSTRACT: A series of diethyl 2-(4,5-dimethoxycarbonyl-1H-1,2,3-triazol-1-yl)alkylphosphonates was synthesised from ω-azidoalkylphosphonates and dimethyl acetylenedicarboxylate and was further transformed into the respective diamides, dihydrazides, and 5,6-dihydro-1H-[1,2,3]triazolo[4,5-d]pyridazine-4,7-diones as phosphonate analogues of acyclic nucleosides having nucleobases replaced with substituted 1,2,3-triazoles. All compounds containing P–C–C–triazole or P–C–C–CH(2)–triazole moieties exist in single conformations in which the diethoxyphosphoryl and substituted 1,2,3-triazolyl or substituted (1,2,3-triazolyl)methyl groups are oriented anti. All phosphonates were evaluated in vitro for activity against a variety of DNA and RNA viruses. None of the compounds were endowed with antiviral activity. They were not cytostatic at 100 μM. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00706-013-1137-x) contains supplementary material, which is available to authorized users.


title: Inhibition of hepatitis B virus gene expression and replication by endoribonuclease-prepared siRNA

text: Abstract Endoribonuclease-prepared siRNA (esiRNA) is an alternative tool to chemical synthetic siRNA for gene silencing. Since esiRNAs are directed against long target sequences, the genetic variations in the target sequences will have little influence on their effectiveness. The ability of esiRNAs to inhibit hepatitis B virus (HBV) gene expression and replication was tested. EsiRNAs targeting the coding region of HBV surface antigen (HBsAg) and the nucleocapsid (HBcAg) inhibited specifically the expression of HBsAg and HBcAg when cotransfected with the respective expression plasmids. Both esiRNAs reduced the HBV transcripts and replication intermediates in transient transfected cells and cells with HBV genomes integrated stably. Compared with synthetic siRNA, esiRNA targeting HBsAg was less effective than the selected synthetic siRNA in terms of the inhibition of HBV gene expression and replication. However, while the ability of synthetic siRNAs for specific gene silencing was impaired strongly by the nucleotide substitutions within the target sequences. The efficiency of gene silencing by esiRNAs was not influenced by sequence variation. The transfection of esiRNA did not induce interferon-stimulated genes (ISGs) like STAT1 and ISG15, indicating the absence of off-target effects. In general, esiRNAs strongly inhibited HBV gene expression and replication and may have an advantage against HBV strains which are variable genetically.


title: Does recombinant human erythropoietin administration in critically ill COVID‐19 patients have miraculous therapeutic effects?

text: An 80‐year‐old man with multiple comorbidities presented to the emergency department with tachypnea, tachycardia, fever, and critically low O(2) saturation and definitive chest computerized tomography scan findings in favor of COVID‐19 and positive PCR results in 48 hours. He received antiviral treatment plus recombinant human erythropoietin (rhEPO) due to his severe anemia. After 7 days of treatment, he was discharged with miraculous improvement in his symptoms and hemoglobin level. We concluded that rhEPO could attenuate respiratory distress syndrome and confront the severe acute respiratory syndrome coronavirus 2 virus through multiple mechanisms including cytokine modulation, antiapoptotic effects, leukocyte release from bone marrow, and iron redistribution away from the intracellular virus.


title: Effect of facemasks on empathy and relational continuity: a randomised controlled trial in primary care

text: BACKGROUND: There is limited evidence to support the use of facemasks in preventing infection for primary care professionals. Negative effects on communication has been suggested when the physician wears a facemask. As communication skills and doctor patient relationship are essential to primary care consultations, the effects of doctor’s facemask wearing were explored. METHOD: A randomised controlled study was conducted in primary care to explore the effects of doctors wearing facemasks on patients’ perception of doctors’ empathy, patient enablement and patient satisfaction. Primary care doctors were randomized to mask wearing and non mask wearing clinical consultations in public primary care clinics in Hong Kong. Patients’ views were gathered using the Consultation and Relational Empathy (CARE) Measure, Patient Enablement Instrument (PEI) and an overall satisfaction rating scale. The effects of face mask wearing were investigated using multilevel (hierarchical) modelling. RESULTS: 1,030 patients were randomised to doctor-mask wearing consultations (n = 514) and non mask wearing consultations (n = 516). A significant and negative effect was found in the patients’ perception of the doctors’ empathy (CARE score reduction -0.98, p-value = 0.04). In the more established doctor-patient relationship, the effect of doctors’ mask wearing was more pronounced (CARE score reduction -5.67, p-value = 0.03). CONCLUSION: This study demonstrates that when doctors wearing a facemask during consultations, this has a significant negative impact on the patient’s perceived empathy and diminish the positive effects of relational continuity. Consideration should be taken in planning appropriate use of facemasks in infectious disease policy for primary care and other healthcare professionals at a national, local or practice level. CLINICAL TRIAL REGISTRATION: This trial was registered on Chinese Clinical Trial Register (ChiCTR). Registration no.: ChiCTR-TTRCC-12002519. URL: http://www.chictr.org/en/proj/show.aspx?proj=3486. Due to administrative error, registration of trial did not take place until after the trial started on 1(st) August 2011 and registration number was released on 21(st) September 2012.


title: Multiplex reverse transcription loop-mediated isothermal amplification combined with nanoparticle-based lateral flow biosensor for the diagnosis of COVID-19

text: The ongoing global pandemic (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a huge public health issue. Hence, we devised a multiplex reverse transcription loop-mediated isothermal amplification (mRT-LAMP) coupled with a nanoparticle-based lateral flow biosensor (LFB) assay (mRT-LAMP-LFB) for diagnosing COVID-19. Using two LAMP primer sets, the ORF1ab (opening reading frame 1a/b) and N (nucleoprotein) genes of SARS-CoV-2 were simultaneously amplified in a single-tube reaction, and detected with the diagnosis results easily interpreted by LFB. In presence of FITC (fluorescein)-/digoxin- and biotin-labeled primers, mRT-LAMP produced numerous FITC-/digoxin- and biotin-attached duplex amplicons, which were determined by LFB through immunoreactions (FITC/digoxin on the duplex and anti-FITC/digoxin on the test line of LFB) and biotin/treptavidin interaction (biotin on the duplex and strptavidin on the polymerase nanoparticle). The accumulation of nanoparticles leaded a characteristic crimson band, enabling multiplex analysis of ORF1ab and N gene without instrumentation. The limit of detection (LoD) of COVID-19 mRT-LAMP-LFB was 12 copies (for each detection target) per reaction, and no cross-reactivity was generated from non-SARS-CoV-2 templates. The analytical sensitivity of SARS-CoV-2 was 100% (33/33 oropharynx swab samples collected from COVID-19 patients), and the assay's specificity was also 100% (96/96 oropharynx swab samples collected from non-COVID-19 patients). The total diagnostic test can be completed within 1 h from sample collection to result interpretation. In sum, the COVID-19 mRT-LAMP-LFB assay is a promising tool for diagnosing SARS-CoV-2 infections in frontline public health field and clinical laboratories, especially from resource-poor regions.


title: The impact of the COVID-19 pandemic on marginalized populations in the United States: A research agenda

text: Abstract International and national crises often highlight inequalities in the labor market that disproportionately affect individuals from marginalized backgrounds. The COVID-19 pandemic, and the resulting changes in society due to social distancing measures, has showcased inequities in access to decent work and experiences of discrimination resulting in many of the vulnerable populations in the United States experiencing a much harsher impact on economic and work-related factors. The purpose of this essay is to describe how the COVID-19 pandemic may differentially affect workers of color, individuals from low-income backgrounds, and women in complex ways. First, this essay will discuss disproportionate representation of workers from low-income and racial/ethnic minority backgrounds in sectors most affected by COVID-19. Second, it will discuss the lack of decent work for low-income workers who perform “essential” tasks. Third, this essay will highlight economic and work-related implications of increased discrimination Asian Americans are experiencing in society. Finally, role conflict and stress for women who are managing additional unpaid work, including caretaking responsibilities, while needing to continue to engage in paid work will be examined. A research agenda will be set forth throughout the essay, calling for vocational psychologists to engage in research that fully examines how the COVID-19 pandemic is affecting vulnerable communities.


title: Informed public against false rumor in the social media era: Focusing on social media dependency

text: Abstract This study explores how the public’s belief in false rumors about Middle East Respiratory Syndrome that spread across South Korea related to their accuracy-oriented information seeking as well as the moderating effects of people’s reasons for using social networking services (SNS). The survey results show that perceived credibility of false rumors did not affect accuracy-oriented information seeking. However, a significant result was shown in the moderating effect, such that SNS informational dependency interacted with false rumor credibility on accuracy-oriented information seeking. Overall, this study specifically identifies and discusses differences in SNS dependency and accuracy-oriented information seeking in the context of rumor communication to examine the construction of an informed public. Theoretical contributions of this study are discussed.


title: Conduite à tenir devant une diarrhée aiguë. Étiologies

text: Résumé Les diarrhées aiguës constituent un problème de santé publique du fait de leur grande fréquence. Leur origine est presque toujours infectieuse et leur évolution spontanément résolutive, le plus souvent en moins de 3 jours. Seul 1 % des diarrhées nécessite d'emblée des explorations complémentaires, notamment des examens de selles, car leur présentation clinique évoque une colite aiguë sous-jacente (selles sanglantes, douleurs abdominales circonscrites), du fait d'un terrain fragile sous-jacent avec un risque immédiat pour le malade, ou d'un contexte particulier (séjour sous les tropiques…). Ces examens de selles doivent être orientés afin de guider le biologiste et améliorer la rentabilité des prélèvements, qui s'avère sinon très faible et coûteuse à l'échelle d'une population. Une antibiothérapie empirique basée essentiellement sur les fluoroquinolones est ensuite licite dans ces cas sélectionnés, en attendant les résultats des examens. Ces explorations sont aussi justifiées lorsque la diarrhée persiste au-delà de 3 jours. Enfin, lorsque l'épisode se prolonge au-delà de 5 jours, avec des prélèvements de selles négatifs, un avis spécialisé est nécessaire. Ainsi, seule une petite proportion de ces diarrhées aiguës va nécessiter une endoscopie, permettant de parler ainsi de colite ou de rectocolite. Au plan thérapeutique, la réhydratation précoce chez l'enfant reste d'actualité car elle a prouvé son efficacité en termes de mortalité depuis plus de deux décennies, principalement dans les pays en voie de développement. Abstract Acute diarrheas are a common disease, and their high frequency constitutes an important problem in terms of public health. Most of the time, they have an infectious origin and spontaneous complete recovery is achieved within less than three days. In practice, history of diarrhea, physical examination and environmental identification are the main points for selecting patients who will need medical explorations. Only 1% of patients need immediate laboratory complementary investigations, i.e., stool analysis, either because their symptomatology indicates potential underlying acute colitis (bloody stools, localized abdominal pain), or when there is an underlying frail condition associated with an immediate risk for the patient, or in case of a particular context such a stay in a tropical area. The practitioner has to inform the biologist on all symptoms and relevant information so as to optimize the analysis and its cost-effectiveness. Until the laboratory results are available, such selected patients require antibiotic treatment (quinolones). These investigations are also needed in case of >3-day persistent diarrhea. When stool samples are free of bacteria or parasite, and when acute diarrhea persists more than 5 days, a specialist should be visited. Thus, only a small proportion of patients with acute diarrhea will undergo endoscopy, probably cases of colitis or recto colitis. Early re-hydration remains the preferential treatment of acute diarrhea in children since, for more than two decades, it has demonstrated its efficacy in reducing mortality, particularly in developing countries.


title: An Otofuke-like virus associated with diarrhoea. Case report and electronmicroscopic study

text: Virus particles similar to Otofuke virus have been found, together with rotaviruses and astroviruses, by electronmicroscopy in faeces from an infant with diarrhoea in Northern Ireland. Previously Otofuke virus has been found only in Japan whence it may have been carried to this country by a businessman.


A tripartite approach can seek to optimize breast cancer management during a pandemic – Real‐Time experience of a developing breast oncology unit in Singapore


title: Contributions of dermatologists to COVID‐19 research: a brief systematic review

text: Coronavirus Disease 2019 (COVID‐19) has been declared a pandemic. We conducted a systematic review to reveal the contribution of dermatologists in COVID‐19 research. 298 articles were included and classified into cutaneous manifestations of COVID‐19, operating experience against COVID‐19, mechanisms and treatment of COVID‐19, disinfection and personal protective equipment(PPE)‐related skin diseases and other topics. The value of these articles and their impact on clinical impact were discussed and we hope that dermatologists can have a better understanding of these areas from this study. This article is protected by copyright. All rights reserved.


COVID-19 and the quality use of medicines: evidence, risks and fads


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title: The need for accurate D‐dimer reporting in COVID‐19: Communication from the ISTH SSC on Fibrinolysis

text: The coronavirus disease 2019 (COVID‐19) pandemic continues to claim many lives across the world. In the attempts to identify a reliable prognostic indicator, marked elevation of D‐dimer has been a strong contender.(1,2) In many studies, D‐dimers have consistently been shown to be the most significant marker for illness severity and death risk prediction.(3,4) Despite the usefulness of this fibrinolytic marker, along with a recent letter by Gris et al.,(5) we note several problems across the medical literature with D‐dimer reporting creating confusion and potentially misleading data interpretation.


title: Public behavior change, perceptions, depression, and anxiety in relation to the COVID-19 outbreak

text: BACKGROUND: The COVID-19 has spread rapidly and world-widely, which elicits public panic and psychological problems. Public protective behaviors and perception play crucial roles in controlling the spread of illness and psychological status. METHODS: We conducted a cross-sectional online survey in the hardest-hit Hubei province and other areas in China affected by COVID-19 outbreak. Questions about their basic information, the perception of the COVID-19 outbreak, recent preventive or avoidance behaviors, and self-reported mental health scales including the Patient Health Questionnaire (PHQ-9) and Self-Rating Anxiety Scale (SAS) were included. Binary logistic regressions were used to investigate the association between personal variables/perceptions and psychological distress. RESULTS: 6,261 people were included for analysis, with 3,613 (57.7%) in Hubei province (1,743 in Wuhan). A majority of people have adopted preventive and avoidance behaviors. People from Hubei, with contact history, and people who or whose family members were infected had much higher depression or anxiety prevalence. Providing truthful and sufficient information, informing the public about the severity of the disease, and perceptions that the outbreak will be control by protective behaviors were associated with lower depression and anxiety prevalence. CONCLUSIONS: Assessing the public response, perception, and psychological burden during the outbreak may help improve public health recommendations and deliver timely psychological intervention. Further researches can focus on the psychological status of a specialized group to identify ways for better support based on public response and psychological demand.


title: Resilience strategies to manage psychological distress amongst healthcare workers during the COVID‐19 pandemic: a narrative review

text: The COVID‐19 pandemic marks an extraordinary global public health crisis unseen in the last century, with its rapid spread worldwide and associated mortality burden. The longevity of the crisis, and disruption to normality is unknown. With COVID‐19 set to be a chronic health crisis, clinicians will be required to maintain a state of high alert for an extended period. The support received before and during an incident is likely to influence whether clinicians experience psychological growth or injury. An abundance of information is emerging on disease epidemiology, pathogenesis and infection control prevention. However, literature on interventions for supporting the psychological wellbeing of healthcare workers during disease outbreaks is limited. This article summarises the available management strategies to increase resilience in healthcare workers during the COVID‐19 pandemic and beyond. It focuses on self care and organisational justice. It highlights various individual as well as organisational strategies. With the success of slowing disease spread in many countries to date, and reduced workload due to limitations on elective surgery in many institutions, there is more time and opportunity to be proactive in implementing measures to mitigate or minimise potential adverse psychological effects and improve, restore and preserve the wellbeing of the workforce now and for years to come. The purpose of this review is to review available literature on strategies for minimising the psychological impact of the COVID‐19 pandemic on clinicians and to identify proactive holistic approaches which may be beneficial for healthcare workers both for the current crisis and into the future.


title: Proteomics informed by transcriptomics reveals Hendra virus sensitizes bat cells to TRAIL-mediated apoptosis

text: BACKGROUND: Bats are a major reservoir of emerging infectious viruses. Many of these viruses are highly pathogenic to humans however bats remain asymptomatic. The mechanism by which bats control viral replication is unknown. Here we utilize an integrated approach of proteomics informed by transcriptomics to compare the response of immortalized bat and human cells following infection with the highly pathogenic bat-borne Hendra virus (HeV). RESULTS: The host response between the cell lines was significantly different at both the mRNA and protein levels. Human cells demonstrated minimal response eight hours post infection, followed by a global suppression of mRNA and protein abundance. Bat cells demonstrated a robust immune response eight hours post infection, which led to the up-regulation of apoptosis pathways, mediated through the tumor necrosis factor-related apoptosis inducing ligand (TRAIL). HeV sensitized bat cells to TRAIL-mediated apoptosis, by up-regulating death receptor transcripts. At 48 and 72 hours post infection, bat cells demonstrated a significant increase in apoptotic cell death. CONCLUSIONS: This is the first study to comprehensively compare the response of bat and human cells to a highly pathogenic zoonotic virus. An early induction of innate immune processes followed by apoptosis of virally infected bat cells highlights the possible involvement of programmed cell death in the host response. Our study shows for the first time a side-by-side high-throughput analysis of a dangerous zoonotic virus in cell lines derived from humans and the natural bat host. This enables a way to search for divergent mechanisms at a molecular level that may influence host pathogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0532-x) contains supplementary material, which is available to authorized users.


title: Antibody-Based Sensors: Principles, Problems and Potential for Detection of Pathogens and Associated Toxins

text: Antibody-based sensors permit the rapid and sensitive analysis of a range of pathogens and associated toxins. A critical assessment of the implementation of such formats is provided, with reference to their principles, problems and potential for ‘on-site’ analysis. Particular emphasis is placed on the detection of foodborne bacterial pathogens, such as Escherichia coli and Listeria monocytogenes, and additional examples relating to the monitoring of fungal pathogens, viruses, mycotoxins, marine toxins and parasites are also provided.


title: SÍNDROME DE GUILLAIN-BARRÉ TRAS INFECCIÓN POR COVID-19

text: RESUMEN La infección por COVID-19 declarada pandemia en el 2020 y cuya gravedad está relacionada con el desarrollo de distrés pulmonar, también presenta afectación a otros niveles incluyendo cuadros neurológicos que hasta el momento han pasado más desapercibidos. Nosotros presentamos un caso de un varón de 77 años con la variante de debilidad faringo-cervico-braquial del Síndrome de Guillain Barré tras un ingreso por neumonía bilateral por COVID-19.


title: The Role of Selenium in Health and Disease: Emerging and Recurring Trends

text: In this Special Issue of Nutrients, "The Role of Selenium in Health and Disease" covers diverse diseases in the 8 original research articles and 2 reviews, such as cardiovascular disorders (CVD), metabolic syndrome, obesity, cancer, and viral infection, and highlights novel potential biomarkers of disease risk and prognosis [...].


title: Decreased angiogenic and increased apoptotic activities of bone microvascular endothelial cells in patients with glucocorticoid-induced osteonecrosis of the femoral head

text: BACKGROUND: Glucocorticoid-induced osteonecrosis of the femoral head (ONFH) is closely associated with the dysfunction of the bone microvascular endothelial cells (BMECs). The present study investigated the angiogenic and apoptotic activity of the BMECs in glucocorticoid-induced ONFH. METHODS: This study enrolled a total of 12 patients, six of whom were assigned to the ONFH group whereas the other six served as the control group. The ONFH group was composed of patients with glucocorticoid-induced ONFH while the control group had femoral neck fractures. BMECs were isolated from the subchondral region of the femoral head. Cell proliferation, cell viability, tube formation assay, Transwell assay, TUNEL assay, and Western blot analysis were performed. RESULTS: BMECs of the two groups were successfully isolated and identified. No significant differences were noticed in BMECs proliferation between the two groups. However, compared to the control, cell viability, tube formation, and migration of BMECs were significantly decreased and the number of TUNEL positive cells was markedly increased in the ONFH group. In the ONFH group, it was also noted that the amount of Bax and cleaved-caspase3 was elevated while that of Bcl-2 was reduced. CONCLUSION: The findings of our study revealed that BMECs obtained from the glucocorticoid-induced ONFH patients had decreased angiogenic and increased apoptotic activities, which could explain the pathogenesis and progression of glucocorticoid-induced ONFH.


title: Tension pneumothorax in a patient with COVID-19

text: A 36-year-old man was brought to the emergency department with suspected COVID-19, following a 3-week history of cough, fevers and shortness of breath, worsening suddenly in the preceding 4 hours. On presentation he was hypoxaemic, with an SpO(2) of 88% on 15 L/min oxygen, tachycardic and had no audible breath sounds on auscultation of the left hemithorax. Local guidelines recommended that the patient should be initiated on continuous positive airway pressure while investigations were awaited, however given the examination findings an emergency portable chest radiograph was performed. The chest radiograph demonstrated a left-sided tension pneumothorax. This was treated with emergency needle decompression, with good effect, followed by chest drain insertion. A repeat chest radiograph demonstrated lung re-expansion, and the patient was admitted to a COVID-19 specific ward for further observation. This case demonstrates tension pneumothorax as a possible complication of suspected COVID-19 and emphasises the importance of thorough history-taking and clinical examination.


title: Efficacy and safety of Chinese patent medicine injection for COVID-19: A protocol for systematic review and meta-analysis

text: BACKGROUND: Corona Virus Disease 2019 (COVID-19) has caused a worldwide epidemic since its discovery. The outbreak of virus infection has aroused great concern of the World Health Organization (WHO). COVID-19 is highly infectious and has a high infection rate. So far, no specific drug has been found to cure it. China as one of the first countries attacked by epidemic has shown outstanding in fighting against the COVID-19. The contribution of traditional Chinese medicine can not be ignored. As a kind of representative of traditional Chinese medicine, the Chinese patent medicine injection has significant effect in reducing the clinical symptoms of patients and preventing the deterioration of the disease. However, there is no systematic review of its efficacy and safety. The purpose of this study is to evaluate the efficacy and safety of Chinese patent medicine injection in the treatment of COVID-19. METHODS: All randomized controlled trials of Chinese patent medicine injection for COVID-19 will be included. The following electronic databases will be searched: PubMed, Web of Science, the Cochrane Library, EMBASE, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database, Chinese Biomedical Literature database and some clinical trial registration websites. Two researchers will independently screen titles, abstracts, full texts, and extract data, then assess the bias risk of each study. We will conduct meta-analyses to assess all the available evidence of the efficacy and safety. RESULTS: Systematic review of current evidence will be provided from the indexes of efficacy and safety. CONCLUSION: Evidence regarding the efficacy and safety of Chinese patent medicine injection in the treatment of COVID-19 will be provided to clinicians. PROSPERO registration number: CRD42020182725


title: Angiotensin converting enzyme-2 (ACE2) and its possible roles in hypertension, diabetes and cardiac function

text: Angiotensin converting enzyme-2 (ACE2) is a recently described homologue of the vasoactive peptidase, angiotensin converting enzyme (ACE). Like ACE, ACE2 is an integral (type I) membrane zinc metallopeptidase, which exists as an ectoenzyme. ACE2 is less widely distributed than ACE in the body, being expressed at highest concentrations in the heart, kidney and testis. ACE2 also differs from ACE in its substrate specificity, functioning exclusively as a carboxypeptidase rather than a peptidyl dipeptidase. A key role for ACE2 appears to be emerging in the conversion of angiotensin II to angiotensin (1–7), allowing it to act as a counter-balance to the actions of ACE. ACE2 has been localised to the endothelial and epithelial cells of the heart and kidney where it may have a role at the cell surface in hydrolysing bioactive peptides such as angiotensin II present in the circulation. A role for ACE2 in the metabolism of other biologically active peptides also needs to be considered. ACE2 also serendipitously appears to act as a receptor for the severe acute respiratory syndrome (SARS) coronavirus. Studies usingace2 (−/−) mice, and other emerging studiesin vivo andin vitro, have revealed that ACE2 has important functions in cardiac regulation and diabetes. Together with its role as a SARS receptor, ACE2 is therefore likely to be an important therapeutic target in a diverse range of disease states.


title: Thalassemia in the emergency department: special considerations for a rare disease

text: Thalassemia is characterized by a defect in the synthesis of one or more of the globin subunits of hemoglobin. This defect results in imbalance in the α/β-globin chain ratio, ineffective erythropoiesis, chronic hemolytic anemia, and iron overload. With advances in diagnosis, treatment, and transfusion support, the prognosis of patients with thalassemia has improved over the past few decades. An increasing number of patients with thalassemia is living with long-term complications, including cardiomyopathy, chronic liver disease, endocrinopathy, and infections. In this paper, we review common complications that bring the patient with thalassemia to urgent or emergent medical attention. We also discuss the aspects of emergency care that are most relevant while caring for the patient with thalassemia in the emergency department.


Pandemia de Covid-19 y transformación digital en Cuidados Intensivos


Is the use of laparoscopy in a COVID‐19 epidemic free of risk?


title: The epidemiology and etiology of influenza‐like illness in Chinese children from 2008 to 2010

text: Influenza‐like illness can be caused by a wide range of respiratory viruses. In order to investigate the epidemiology of viral pathogens related to influenza‐like illness in children of Wuhan, the largest city in central China, throat swab samples were collected from 1,472 young patients, from July 2008 to June 2010, before and after the occurrence of the 2009 pandemic influenza A (H1N1) virus (pH1N1). It was found that 923 patients (62.7%) were positive for at least 1 virus and 90 patients (9.8%) were detected for multiple (≥2) respiratory viruses by real‐time PCR detection of 16 viruses. Seasonal influenza A virus was the predominant pathogen among all the 16 viruses with a positive rate of 13.3% (196/1,472), which was followed by pH1N1 (159/1,472). It was also noted that the viral distribution pattern in Wuhan changed upon the introduction of the pH1N1 virus. J. Med. Virol. 84:672–678, 2012. © 2011 Wiley Periodicals, Inc.


title: Norovirus Regulation of the Innate Immune Response and Apoptosis Occurs via the Product of the Alternative Open Reading Frame 4

text: Small RNA viruses have evolved many mechanisms to increase the capacity of their short genomes. Here we describe the identification and characterization of a novel open reading frame (ORF4) encoded by the murine norovirus (MNV) subgenomic RNA, in an alternative reading frame overlapping the VP1 coding region. ORF4 is translated during virus infection and the resultant protein localizes predominantly to the mitochondria. Using reverse genetics we demonstrated that expression of ORF4 is not required for virus replication in tissue culture but its loss results in a fitness cost since viruses lacking the ability to express ORF4 restore expression upon repeated passage in tissue culture. Functional analysis indicated that the protein produced from ORF4 antagonizes the innate immune response to infection by delaying the upregulation of a number of cellular genes activated by the innate pathway, including IFN-Beta. Apoptosis in the RAW264.7 macrophage cell line was also increased during virus infection in the absence of ORF4 expression. In vivo analysis of the WT and mutant virus lacking the ability to express ORF4 demonstrated an important role for ORF4 expression in infection and virulence. STAT1-/- mice infected with a virus lacking the ability to express ORF4 showed a delay in the onset of clinical signs when compared to mice infected with WT virus. Quantitative PCR and histopathological analysis of samples from these infected mice demonstrated that infection with a virus not expressing ORF4 results in a delayed infection in this system. In light of these findings we propose the name virulence factor 1, VF1 for this protein. The identification of VF1 represents the first characterization of an alternative open reading frame protein for the calicivirus family. The immune regulatory function of the MNV VF1 protein provide important perspectives for future research into norovirus biology and pathogenesis.


title: Nanoparticle-Based Vaccines Against Respiratory Viruses

text: The respiratory mucosa is the primary portal of entry for numerous viruses such as the respiratory syncytial virus, the influenza virus and the parainfluenza virus. These pathogens initially infect the upper respiratory tract and then reach the lower respiratory tract, leading to diseases. Vaccination is an affordable way to control the pathogenicity of viruses and constitutes the strategy of choice to fight against infections, including those leading to pulmonary diseases. Conventional vaccines based on live-attenuated pathogens present a risk of reversion to pathogenic virulence while inactivated pathogen vaccines often lead to a weak immune response. Subunit vaccines were developed to overcome these issues. However, these vaccines may suffer from a limited immunogenicity and, in most cases, the protection induced is only partial. A new generation of vaccines based on nanoparticles has shown great potential to address most of the limitations of conventional and subunit vaccines. This is due to recent advances in chemical and biological engineering, which allow the design of nanoparticles with a precise control over the size, shape, functionality and surface properties, leading to enhanced antigen presentation and strong immunogenicity. This short review provides an overview of the advantages associated with the use of nanoparticles as vaccine delivery platforms to immunize against respiratory viruses and highlights relevant examples demonstrating their potential as safe, effective and affordable vaccines.


title: Development of Small‐Molecule Antivirals for Ebola

text: Ebola hemorrhagic fever is a deadly disease caused by infection with one of the Ebola virus species. Although a significant progress has recently been made in understanding of Ebola virus biology and pathogenesis, development of effective anti‐Ebola treatments has not been very productive, compared to other areas of antiviral research (e.g., HIV and HCV infections). No approved vaccine or medicine is available for Ebola but several are currently under development. This review summarises attempts in identification, evaluation, and development of small‐molecule candidates for treatment of Ebola viral disease, including the most promising experimental drugs brincidofovir (CMX001), BCX4430, and favipiravir (T‐705).


title: Analysis of the Electricity Demand Trends amidst the COVID-19 Coronavirus Pandemic

text: This paper investigates the impact of COVID-19 and the global pandemic on the energy sector dynamics. Hourly electricity demand data was collected and analyzed for the province of Ontario. It is evident that health-related pandemics have a detrimental and direct influence on the concept of the smart city. This is manifested through various social, economic, environmental, technological and energy-related changes. The overall electricity demand of the province for the month of April of this year amidst pandemic conditions declined by 14%, totaling 1,267 GW. A unique trend of reciprocating energy demand exists throughout the week. The post-COVID-19 indicates higher energy demand in the earlier part of the week and a lower demand in the latter part of the week. Pre-pandemic, the days of highest electricity demand were in the latter part of the work week (Wed-Fri) in addition to the weekend. Post-pandemic, the highest electricity demand occurred in the earlier part of the week (Mon-Tue). Hourly electricity demand shows a clear curve flattening during the pandemic, especially during peak hours of 7 – 11 in the morning and 5 – 7 in the evening, resulting in significant demand reductions during these periods. Lastly, due to COVID-19, GHG emission reductions of 40,000 tonnes of CO(2)e were achieved along with savings of $131,844 for the month of April.


title: Middle East respiratory syndrome coronavirus in children

text: The Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). The disease is reported mainly in adults. Data in children are scarce. The disease caused by MERS-CoV in children presents with a wide range of clinical manifestations, and it is associated with a lower mortality rate compared with adults. Poor outcome is observed mainly in admitted patients with medical comorbidities. We report a new case of MERS-CoV infection in a 9-month-old child complicated by severe respiratory symptoms, multi-organ dysfunction, and death. We reviewed the literature in an attempt to characterize the mode of presentation, the risk factors, and outcome of MERS-CoV infection in the pediatric population.


docid: jgrilsfc

title: Determination of host cell proteins constituting the molecular microenvironment of coronavirus replicase complexes by proximity-labeling

text: Positive-sense RNA viruses hijack intracellular membranes that provide niches for viral RNA synthesis and a platform for interactions with host proteins. However, little is known about host factors at the interface between replicase complexes and the host cytoplasm. We engineered a biotin ligase into a coronaviral replication/transcription complex (RTC) and identified >500 host proteins constituting the RTC microenvironment. siRNA-silencing of each RTC-proximal host factor demonstrated importance of vesicular trafficking pathways, ubiquitin-dependent and autophagy-related processes, and translation initiation factors. Notably, detection of translation initiation factors at the RTC was instrumental to visualize and demonstrate active translation proximal to replication complexes of several coronaviruses. Collectively, we establish a spatial link between viral RNA synthesis and diverse host factors of unprecedented breadth. Our data may serve as a paradigm for other positive-strand RNA viruses and provide a starting point for a comprehensive analysis of critical virus-host interactions that represent targets for therapeutic intervention.


Barriers to Telemedicine Implementation in Southwest Tribal Communities During COVID‐19


title: Diagnosis of COVID‐19 pneumonia despite missing detection of viral nucleic acid and initially inconspicuous radiologic findings

text: The diagnosis of coronavirus disease 2019 (COVID‐19) is mainly based on a positive SARS‐CoV‐2 polymerase chain reaction (PCR) result. PCR samples are obtained from upper or lower respiratory tract specimens. However, the sensitivity of PCR is known to have some limitations. We report on a patient who was admitted to our hospital with dyspnea, fever, cough and history of contact to a SARS‐CoV‐2 infected relative. The initial chest computed tomography (CT) showed only minimal changes and SARS‐CoV‐2 PCR from a nasopharyngeal swab sample was negative. PCR results obtained from further nasopharyngeal swabs, qualified sputum samples, and from a lower respiratory tract specimen also remained negative. At day 13 after admission, a second chest CT showed radiological findings suspicious for viral pneumonia. Finally, serologic results showed high levels of IgG and IgA antibodies against the S1 domain of the SARS‐CoV‐2 spike protein and the patient was diagnosed with COVID‐19 pneumonia. This article is protected by copyright. All rights reserved.


docid: msqhnyhw

title: Serological evidence of MERS-CoV and HKU8-related CoV co-infection in Kenyan camels

text: Dromedary camels are important reservoir hosts of various coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) that cause human infections. CoV genomes regularly undergo recombination during infection as observed in bat SARS-related CoVs. Here we report for the first time that only a small proportion of MERS-CoV receptor-binding domain positive (RBD) of spike protein positive camel sera in Kenya were also seropositive to MERS-CoV nucleocapsid (NP). In contrast, many of them contain antibodies against bat HKU8-related (HKU8r)-CoVs. Among 584 camel samples that were positive against MERS-CoV RBD, we found only 0.48 (8.22%) samples were also positive for NP. Furthermore, we found bat HKU8r-CoV NP antibody in 73 (12.5%) of the MERS-CoV RBD positive and NP negative samples, yet found only 3 (0.43%) of the HKU8r-CoV S1 antibody in the same samples. These findings may indicate co-infection with MERS-CoV and a HKU8r-CoV in camels. It may also raise the possibility of the circulation of a recombinant coronavirus virus with the spike of MERS-CoV and the NP of a HKU8r-CoV in Kenya. We failed to find molecular evidence of an HKU8r-CoV or a putative recombinant virus. Our findings should alert other investigators to look for molecular evidence of HKU8r-CoV or recombinants.


title: Making the Mark: The Role of Adenosine Modifications in the Lifecycle of RNA Viruses

text: Viral epitranscriptomics is a newly emerging field that has identified unique roles for RNA modifications in modulating lifecycles of RNA viruses. Despite the observation of a handful of modified viral RNAs five decades ago, very little was known about how these modifications regulate viral lifecycles, until recently. Here we review the pro- and anti-viral effects of methyl-6-adenosine in distinct viral life cycles, the role of 2′ O-methyl modifications in RNA stability and innate immune sensing, and functions of adenosine to inosine modifications in retroviral life cycles. With roles for over 100 modifications in RNA still unknown, this is a rapidly emerging field that is destined to suggest novel antiviral therapies.


title: Spatio-Temporal Patterns of the 2019-nCoV Epidemic at the County Level in Hubei Province, China

text: Understanding the spatio-temporal characteristics or patterns of the 2019 novel coronavirus (2019-nCoV) epidemic is critical in effectively preventing and controlling this epidemic. However, no research analyzed the spatial dependency and temporal dynamics of 2019-nCoV. Consequently, this research aims to detect the spatio-temporal patterns of the 2019-nCoV epidemic using spatio-temporal analysis methods at the county level in Hubei province. The Mann–Kendall and Pettitt methods were used to identify the temporal trends and abrupt changes in the time series of daily new confirmed cases, respectively. The local Moran’s I index was applied to uncover the spatial patterns of the incidence rate, including spatial clusters and outliers. On the basis of the data from January 26 to February 11, 2020, we found that there were 11 areas with different types of temporal patterns of daily new confirmed cases. The pattern characterized by an increasing trend and abrupt change is mainly attributed to the improvement in the ability to diagnose the disease. Spatial clusters with high incidence rates during the period were concentrated in Wuhan Metropolitan Area due to the high intensity of spatial interaction of the population. Therefore, enhancing the ability to diagnose the disease and controlling the movement of the population can be confirmed as effective measures to prevent and control the regional outbreak of the epidemic.


docid: ldvspikx

title: Pattern recognition receptors in equine endotoxaemia and sepsis

text: Pattern recognition receptors (PRRs) on host cells detect pathogens to activate innate immunity which, in turn, initiates inflammatory and adaptive immune responses. Successful activation of PRRs is, therefore, critical to controlling infections and driving pathogen‐specific adaptive immunity, but overactivity of PRRs causes systemic inflammation, which is detrimental to the host. Here we review the PRR literature as it relates to horses and speculate on the role PRRs may play in sepsis and endotoxaemia.


title: A Universal Influenza A and B Duplex Real‐time RT‐PCR Assay

text: A high throughput universal influenza A and B duplex real‐time RT‐PCR was developed to meet effectively the heightened surveillance and diagnostic needs essential in managing influenza infections and outbreaks. Primers and probes, designed to target highly conserved regions of the matrix protein of influenza A and the nucleoprotein of influenza B, were optimized using the high‐throughput LightCycler 480 II system. Analytical sensitivity and specificity were characterized using RNA transcripts diluted serially, archived non‐influenza respiratory viruses, and proficiency test samples. Eighty‐nine clinical samples were tested in parallel against existing influenza A and B monoplex assays. Once validated, the duplex assay was applied prospectively on 2,458 clinical specimens that were later subtyped. In April 2011, the emergence of an influenza B variant necessitated the inclusion of an additional modified probe for influenza B and revalidation of the revised protocol. The lower detection limits of the assay were 50 copies/PCR. There was no cross‐reactivity against any non‐influenza respiratory virus and all proficiency testing materials were identified correctly. The parallel testing revealed a 98.9% overall agreement. Routine application of the assay revealed high sensitivity and specificity for the detection of influenza A/H1N1/2009, A/H3N2 and influenza B. Assay C(q) values correlated well between the pre‐ and post‐revision protocols for influenza A (r(2) = 0.998) and B (r(2) = 0.999). The revised protocol detected three additional novel influenza B variant cases in 200 specimens reported previously as influenza B negative. This in‐house assay offers a highly sensitive and specific option for laboratories seeking to expand their influenza testing capacity. J. Med. Virol. 84:1646–1651, 2012. © 2012 Wiley Periodicals, Inc.


title: PER1 prevents excessive innate immune response during endotoxin-induced liver injury through regulation of macrophage recruitment in mice

text: The severity of acute liver failure (ALF) induced by bacterial lipopolysaccharide (LPS) is associated with the hepatic innate immune response. The core circadian molecular clock modulates the innate immune response by controlling rhythmic pathogen recognition by the innate immune system and daily variations in cytokine gene expression. However, the molecular link between circadian genes and the innate immune system has remained unclear. Here, we showed that mice lacking the clock gene Per1 (Period1) are more susceptible to LPS/d-galactosamine (LPS/GalN)-induced macrophage-dependent ALF compared with wild-type (WT) mice. Per1 deletion caused a remarkable increase in the number of Kupffer cells (KCs) in the liver, resulting in an elevation of the levels of pro-inflammatory cytokines after LPS treatment. Loss of Per1 had no effect on the proliferation or apoptosis of macrophages; however, it enhanced the recruitment of macrophages, which was associated with an increase in CC chemokine receptor 2 (Ccr2) expression levels in monocytes/macrophages. Deletion of Ccr2 rescued d-GalN/LPS-induced liver injury in Per1(−/−) mice. We demonstrated that the upregulation of Ccr2 expression by Per1 deletion could be reversed by the synthetic peroxisome proliferator-activated receptor gamma (PPAR-γ) antagonist GW9662. Further analysis indicated that PER1 binds to PPAR-γ on the Ccr2 promoter and enhanced the inhibitory effect of PPAR-γ on Ccr2 expression. These results reveal that Per1 reduces hepatic macrophage recruitment through interaction with PPAR-γ and prevents an excessive innate immune response in endotoxin-induced liver injury.


Primer caso de infección neonatal por SARS-CoV-2 en España


Replication and Expression Analysis of PRRSV Defective RNA


title: Decoy ACE2-expressing extracellular vesicles that competitively bind SARS-CoV-2 as a possible COVID-19 therapy

text: The novel strain of coronavirus that appeared in 2019, SARS-CoV-2, is the causative agent of severe respiratory disease, COVID-19, and the ongoing pandemic. As for SARS-CoV that caused the SARS 2003 epidemic, the receptor on host cells that promotes uptake, through attachment of the spike (S) protein of the virus, is angiotensin-converting enzyme 2 (ACE2). In a recent article published by Batlle et al. (Clin. Sci. (Lond.) (2020) 134, 543–545) it was suggested that soluble recombinant ACE2 could be used as a novel biological therapeutic to intercept the virus, limiting the progression of infection and reducing lung injury. Another way, discussed here, to capture SARS-CoV-2, as an adjunct or alternative, would be to use ACE2(+)-small extracellular vesicles (sEVs). A competitive inhibition therapy could therefore be developed, using sEVs from engineered mesenchymal stromal/stem cells (MSCs), overexpressing ACE2.


Novel Mechanistic Insights into Viral Modulation of Immune Receptor Signaling


title: Effects of superspreaders in spread of epidemic

text: Abstract Within the standard SIR model with spatial structure, we propose two models for the superspreader. In one model, superspreaders have intrinsically strong infectiousness. In other model, they have many social connections. By Monte Carlo simulation, we obtain the percolation probability, the propagation speed, the epidemic curve, the distribution of secondary infected and the propagation path as functions of population and the density of superspreaders. By comparing the results with the data of SARS in Singapore 2003, we conclude that the latter model can explain the observation.


title: Combination of western medicine and Chinese traditional patent medicine in treating a family case of COVID-19 in Wuhan

text: In December 2019, an outbreak of novel Coronavirus (2019-nCoV) occurred in Wuhan, Hubei Province, China. By February 14, 2020, it has led to 66 492 confirmed patients in China and high mortality up to ∼2.96% (1123/37 914) in Wuhan. Here we report the first family case of coronavirus disease 2019 (COVID-19) confirmed in Wuhan and treated using the combination of western medicine and Chinese traditional patent medicine Shuanghuanglian oral liquid (SHL). This report describes the identification, diagnosis, clinical course, and management of three cases from a family, suggests the expected therapeutic effects of SHL on COVID-19, and warrants further clinical trials.


title: ACR Statement on Safe Resumption of Routine Radiology Care During the COVID-19 Pandemic

text: The ACR recognizes that radiology practices are grappling with when and how to safely resume routine radiology care during the coronavirus disease 2019 (COVID-19) pandemic. Although it is unclear how long the pandemic will last, it may persist for many months. Throughout this time, it will be important to perform safe, comprehensive, and effective care for patients with and patients without COVID-19, recognizing that asymptomatic transmission is common with this disease. Local idiosyncrasies prevent a single prescriptive strategy. However, general considerations can be applied to most practice environments. A comprehensive strategy will include consideration of local COVID-19 statistics; availability of personal protective equipment (PPE); local, state, and federal government mandates; institutional regulatory guidance; local safety measures; health care worker availability; patient and health care worker risk factors; factors specific to the indication(s) for radiology care; and examination or procedure acuity. An accurate risk-benefit analysis of postponing versus performing a given routine radiology examination or procedure often is not possible due to many unknown and complex factors. However, this is the overriding principle: If the risk of illness or death to a health care worker or patient from health care-acquired COVID-19 is greater than the risk of illness or death from delaying radiology care, the care should be delayed; however, if the opposite is true, the radiology care should proceed in a timely fashion.


title: Establishment of minimal positive-control conditions to ensure brain safety during rapid development of emergency vaccines

text: With the increase in international human and material exchanges, contagious and infectious epidemics are occurring. One of the effective methods of epidemic inhibition is the rapid development and supply of vaccines. Considering the safety of the brain during vaccine development is very important. However, manuals for brain safety assays for new vaccines are not uniform or effective globally. Therefore, the aim of this study is to establish a positive-control protocol for an effective brain safety test to enhance rapid vaccine development. The blood-brain barrier's tight junctions provide selective defense of the brain; however, it is possible to destroy these important microstructures by administering lipopolysaccharides (LPSs), thereby artificially increasing the permeability of brain parenchyma. In this study, test conditions are established so that the degree of brain penetration or brain destruction of newly developed vaccines can be quantitatively identified. The most effective conditions were suggested by measuring time-dependent expressions of tight junction biomarkers (zonula occludens-1 [ZO-1] and occludin) in two types of mice (C57BL/6 and ICR) following exposure to two types of LPS (Salmonella and Escherichia). In the future, we hope that use of the developed positive-control protocol will help speed up the determination of brain safety of novel vaccines.


title: Molecular characterization and pathogenesis of transmissible gastroenteritis coronavirus (TGEV) and porcine respiratory coronavirus (PRCV) field isolates co-circulating in a swine herd

text: TGEV replicates in intestinal enterocytes and causes diarrhea in young pigs. PRCV, a spike (S) gene deletion mutant of TGEV with an altered respiratory tissue tropism, causes mild or subclinical respiratory infections. Comparisons of TGEV and PRCV strains suggest that tropism and pathogenicity are influenced by the S gene and ORF3, respectively. Recently, outbreaks of TGE of reduced virulence were reported in the field. We investigated a similar suspect TGEV outbreak of reduced virulence in nursery pigs from a swine herd in the Midwest. A TGEV strain (BW021898B) was isolated in swine testicular cells from gut contents of a diarrheic pig and three PRCV strains (BW126, BW154, BW155) were isolated from nasal swabs from normal TGEV-seronegative sentinel pigs in contact with the diarrheic pigs. Sequence analysis of the TGEV isolate in the partial S gene and ORF3/3a and ORF3-1/3b revealed high homology with enteropathogenic TGEV strains. Gnotobiotic pig inoculation and histopathological results revealed that this TGEV isolate retained virulence even though in the field outbreak the diarrheal disease was of reduced severity. Sequence analysis of the S gene deletion region of the three PRCV isolates revealed identical deletions between nt 105–752, which differ from deletions previously reported among PRCV strains. The three PRCV isolates had variable sequence changes in ORF 3/3a and ORF 3-1/3b, affecting the ORF size and amino acid sequence. Thus, sequence analysis and pathogenicity studies indicate that this TGEV isolate resembles other enteropathogenic TGEV strains. Therefore, the reduced severity of TGE observed in this herd may be due to the ongoing PRCV infections, which induce antibodies cross-reactive with TGEV and result in decreased disease severity. The results outlined in this study highlight the need to monitor the molecular epidemiology of TGEV/PRCV strains with sensitive differential diagnostic assays, followed by sequence analysis of the critical regions to identify changes and pathogenicity studies to confirm the disease potential of the TGEV isolates.


¿Brotará una mejor salud pública tras la COVID-19?


title: Chapter 8 Quasispecies Dynamics in Disease Prevention and Control

text: Abstract Medical interventions to prevent and treat viral disease constitute evolutionary forces that may modify the genetic composition of viral populations that replicate in an infected host, as well as those that expand at the epidemiological level. Strategies intended to minimize vaccination and treatment failures are proposed, and justified based on fundamental features of viral dynamics. The recommended use of complex, multiepitopic vaccines and combination therapies as early as possible after initiation of an infection falls under the general concept that complexity cannot be combated with simplicity. It follows also that socio-political action to interrupt virus replication and spread as soon as possible is as important as scientifically sound treatment designs to control viral disease on a global scale.


title: Herpes zoster might be an indicator for Latent COVID 19 infection

text: Various cutaneous manifestations have been observed in patients with COVID‐19 infection. Herpes Zoster is a viral skin disease caused by varicella zoster that remains dormant in the dorsal root ganglia of cutaneous nerves following a primary chicken pox infection. In this report we describe two cases COVID infection who first presented with herpes zoster. We are here by suggesting that the clinical presentation of HZ at the time of the current pandemic even in patients giving mild or no suggestive history of upper respiratory symptoms should be considered as an alarming sign for a recent subclinical SARS CoV2 infection. This article is protected by copyright. All rights reserved.


title: COVID-19: asymptomatic carrier transmission is an underestimated problem

text: At the present time, COVID-19 is spreading rapidly [1]. The global prevention and control of COVID-19 is focused on the estimation of the relevant incubation period, basic reproduction number (R(0)), effective reproduction number (R(t)) and death risk. Although the prevention and control of COVID-19 requires a reliable estimation of the relevant incubation period, R(0), R(t) and death risk. Another key epidemiological parameter-asymptomatic ratio that provides strength and range for social alienation strategies of COVID-19, which is widely defined as the proportion of asymptomatic infections among all disease infections. In fact, the ratio of asymptomatic infection is a useful indicator of the burden of disease and a better measurement of the transmissibility of the virus. So far, people have not paid enough attention to asymptomatic carriers. The asymptomatic carriers discussed in this study are recessive infections, that is, those who have never shown symptoms after onset of infection. We will discuss three aspects: detection, infectivity and proportion of healthy carriers.


title: A multiplex one-tube nested real time RT-PCR assay for simultaneous detection of respiratory syncytial virus, human rhinovirus and human metapneumovirus

text: BACKGROUND: Respiratory syncytial virus (RSV), human Rhinovirus (HRV) and human Metapneumo Virus (HMPV) are important viral pathogens causing acute respiratory tract infections in the hospitalized patients. Sensitive and accurate detection of RSV, HRV and HMPV is necessary for clinical diagnosis and treatment. RESULTS: A locked nucleic acid (LNA)-based multiplex closed one-tube nested real-time RT-PCR (mOTNRT-PCR) assay was developed for simultaneous detection of RSV, HRV and HMPV. The sensitivity, specificity, reproducibility and clinical performance of mOTNRT-PCR were evaluated and compared with individual real time PCR (RT-qPCR) assay using clinical samples. The analytical sensitivity of mOTNRT-PCR assay was 5 copies/reaction for RSV, HRV and HMPV, respectively, and no cross-reaction with other common respiratory viruses was observed. The coefficients of variation (CV) of intra-assay and inter-assay were between 0.51 to 3.67%. Of 398 nasopharyngeal aspirates samples tested, 109 (27.39%), 150 (37.69%) and 44 (11.06%) were positive for RSV, HRV and HMPV, respectively, whereas 95 (23.87%), 137 (34.42%) and 38 (9.55%) were positive for RSV, HRV and HMPV, respectively, by individual RT-qPCR assay. Thirty three samples that were positive by mOTNRT-PCR but negative by RT-qPCR were confirmed as true positives by sequencing using reported traditional two-step nested PCR assay. CONCLUSION: mOTNRT-PCR assay reveals extremely higher sensitivity than that of RT-qPCR assay for detecting RSV, HRV and HMPV in clinical settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1061-0) contains supplementary material, which is available to authorized users.


title: Fluorescent Protein Approaches in Alpha Herpesvirus Research

text: In the nearly two decades since the popularization of green fluorescent protein (GFP), fluorescent protein-based methodologies have revolutionized molecular and cell biology, allowing us to literally see biological processes as never before. Naturally, this revolution has extended to virology in general, and to the study of alpha herpesviruses in particular. In this review, we provide a compendium of reported fluorescent protein fusions to herpes simplex virus 1 (HSV-1) and pseudorabies virus (PRV) structural proteins, discuss the underappreciated challenges of fluorescent protein-based approaches in the context of a replicating virus, and describe general strategies and best practices for creating new fluorescent fusions. We compare fluorescent protein methods to alternative approaches, and review two instructive examples of the caveats associated with fluorescent protein fusions, including describing several improved fluorescent capsid fusions in PRV. Finally, we present our future perspectives on the types of powerful experiments these tools now offer.


title: How Hubei fought the virus

text: Doctors on the front line in the Chinese province where the coronavirus outbreak started tell Donna Lu about their experiences treating covid-19


Global Surveillance, National Surveillance, and SARS


Care of patients with hemoglobin disorders during the COVID‐19 pandemic: An overview of recommendations


title: Australia's international health relations in 2003

text: A survey for the year 2003 of significant developments in Australia's official international health relations, and their domestic ramifications, is presented. The discussion is set within the broader context of Australian foreign policy. Sources include official documents, media reports and consultations with officers of the Department of Health and Ageing responsible for international linkages.


title: Detection of Human Bocavirus mRNA in Respiratory Secretions Correlates with High Viral Load and Concurrent Diarrhea

text: Human bocavirus (HBoV) is a parvovirus recently identified in association with acute respiratory infections (ARI). Despite its worldwide occurrence, little is known on the pathogenesis of HBoV infections. In addition, few systematic studies of HBoV in ARI have been conducted in Latin America. Therefore, in order to test whether active viral replication of human bocavirus is associated with respiratory diseases and to understand the clinical impact of this virus in patients with these diseases, we performed a 3-year retrospective hospital-based study of HBoV in outpatients and inpatients with symptoms of Acute Respiratory Infections (ARI) in Brazil. Nasopharyngeal aspirates (NPAs) from 1015 patients with respiratory symptoms were tested for HBoV DNA by PCR. All samples positive for HBoV were tested by PCR for all other respiratory viruses, had HBoV viral loads determined by quantitative real time PCR and, when possible, were tested by RT-PCR for HBoV VP1 mRNA, as evidence of active viral replication. HBoV was detected in 4.8% of patients, with annual rates of 10.0%, 3.0% and 3.0% in 2005, 2006 and 2007, respectively. The range of respiratory symptoms was similar between HBoV-positive and HBoV-negative ARI patients. However, a higher rate of diarrhea was observed in HBoV-positive patients. High HBoV viral loads (>10(8) copies/mL) and diarrhea were significantly more frequent in patients with exclusive infection by HBoV and in patients with detection of HBoV VP1 mRNA than in patients with viral co-infection, detected in 72.9% of patients with HBoV. In summary, our data demonstrated that active HBoV replication was detected in a small percentage of patients with ARI and was correlated with concurrent diarrhea and lack of other viral co-infections.


title: Variable 3’polyadenylation of Wheat yellow mosaic virus and its novel effects on translation and replication

text: BACKGROUND: Polyadenylation influences many aspects of mRNA as well as viral RNA. variable polyadenylation at the 3' end have been reported in RNA viruses. It is interesting to identify the characteristic and potential role of 3' polyadenylation of Wheat yellow mosaic virus (WYMV), which has been reported to contain two genomic RNAs with 3' poly(A) tails and caused severe disease on wheat in East Asia region. METHODS: 3' RACE was used to identify sequences of the 3′ end in WYMV RNAs from naturally infected wheat by WYMV. In vitro translation assay was performed to analyze effect of UTRs of WYMV with or without 3’polyadenylation on translation. In vitro replication mediated by WYMV NIb protein were performed to evaluate effect of variable polyadenylation on replication. RESULTS: Variable polyadenylation in WYMV RNAs was identified via 3′ RACE. WYMV RNAs in naturally infected wheat in China simultaneously present with regions of long, short, or no adenylation at the 3' ends. The effects of variable polyadenylation on translation and replication of WYMV RNAs were evaluated. 5’UTR and 3’UTR of WYMV RNA1 or RNA2 synergistically enhanced the translation of the firefly luciferase (Fluc) gene in in vitro WGE system, whereas additional adenylates had an oppositive effect on this enhancement on translation mediated by UTRs of WYMV. Additional adenylates remarkably inhibited the synthesis of complementary strand from viral genome RNA during the in vitro replication mediated by WYMV NIb protein. CONCLUSIONS: 3' end of WYMV RNAs present variable polyadenylation even no polyadenylation. 3' polyadenylation have opposite effect on translation mediated by UTRs of WYMV RNA1 or RNA2. 3' polyadenylation have negative effect on minus-strand synthesis of WYMV RNA in vitro. Variable polyadenylation of WYMV RNAs may provide sufficient selection on the template for translation and replication. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-019-1130-z) contains supplementary material, which is available to authorized users.


title: Allergie respiratoire et virus

text: Summary Viral respiratory tract infections are a major cause of wheezing in infants. Investigators determined that 80% to 85% of school-aged children with wheezing episodes were tested positive for virus. To more fully understand how viral respiratory tract infections influence asthma, investigators have evaluated the effect of respiratory tract injections on airway symptoms, function, and inflammation. Although the mechanisms by which respiratory viruses enhance lower airway inflammation are not established, cytokines may play a key role in this process. The respiratory epithelial cell is a principal host for respiratory virus replication und is likely to be the first source of cytokines during an acute infection. T cells orchestrate immune responses to both allergens and viruses, and regulate effector cells with virucidal and proinflammalory effects. Although studies demonstrate that virus-specific T cells may contribute to virus-induced lung disease, evidence to define the role of virus-specific T lymphocytes in asthma has not been fully established. Some injections early in life may also have an important immunoregular role in the subsequent development of allergy and asthma. Atopy is characterised by exaggerated Th-2 cell responses to commun allergens with secretion of cytokines such as IL-4 and IL-5 that promote IgE production and eosinophil activation. In contrast, childhood injections typically induce a Th-1 cell response, characterised by secretion oj interferon-γ which enhances the antiviral activities of effector cells. These two types of T cell responses are mutually antagonistic.


title: Effect of essential oils on the immune response to some viral vaccines in broiler chickens, with special reference to Newcastle disease virus

text: Abstract This trial assessed the efficacy of a commercial essential oils (Eos) product on the immune response to vaccination against Newcastle disease (ND) and subsequent challenge with virulent ND virus genotype VII (vNDv genotype VII) by using the following experimental groups of broiler chickens (each group had 21 birds with three replicates in each, n=seven): NC (negative control), PC (positive control), VC (vaccinated), and VTC (vaccinated and treated with EOs). Moreover, in a trial to study the effect of EOs on vNDv genotype VII in vivo as a preventive or therapeutic measure, two additional ND-vaccinated groups were used (PRV: medicated one day before vNDv challenge for 5 days; and TTT: medicated two days post vNDv challenge for 5 days). In addition, the immune-modulatory effect of EOs on the avian influenza (AI), infectious bronchitis (IB) and infectious bursal disease (IBD) vaccines was assessed through the serological response. The use of EOs along with administration of ND vaccines (VTC) revealed lower mortality rate (42.86%), clinical signs and post mortem lesion score (11) comparing to ND vaccines alone (VC) (52.28% mortality and score 15), in addition to lower hemagglutination inhibition (HI) (p<0.05) (6.5±0.46) and viral shedding (10 log 2.28±0.24) titres one week post challenge in comparison with of VC (8.63±0.65 and 10 log 3.29±0.72, respectively). Nevertheless, the EOs mixture (VTC) (1952±28.82) did not significantly (p>0.05) improve growth performance compared to the non-treated birds (NC and VC) (1970±19.56 and 1904±38.66). Essential oils showed an antiviral effect on vNDv in vivo (in chickens) as a preventive measure (PRV) as well as some therapeutic effect (TTT) through decreasing the viral shedding titres (loNC0), mortality rate, and severity of clinical signs and post mortem lesions, in addition to serum malondialdhyde (MDA) level. Regarding the other viruses, the EOs mixture did not improve the immune response to the AI and IB vaccines but significantly (p<0.05) increased the ELISA antibody titre for IBD virus at 28th day of age (2108±341.05). The studied EOs mixture showed an immune stimulating response to ND and IBD vaccines, antiviral effect against ND virus especially if administered before the challenge, however it did not have a growth promoting effect.


title: Locked-down digital work

text: Covid-19 and the related lockdown in many countries made digital work no longer just an option, but the new norm for many office workers who began to make sense of a new range of benefits of digital work tools. Based on my own observations and on observations shared by executives in New Zealand and Europe, I illustrate in this article how the lockdown acted as a facilitator for digital work. Further, I show how the lockdown gave many individuals a flawed impression of digital work, i.e. their experience occurred during exceptional circumstances and led them to draw false conclusions about digital work. I examine some misconceptions of locked-down digital work and discuss the implications of locked-down digital work for research and practice.


title: The Oakville Oil Refinery Closure and Its Influence on Local Hospitalizations: A Natural Experiment on Sulfur Dioxide

text: Background: An oil refinery in Oakville, Canada, closed over 2004–2005, providing an opportunity for a natural experiment to examine the effects on oil refinery-related air pollution and residents’ health. Methods: Environmental and health data were collected for the 16 years around the refinery closure. Toronto (2.5 million persons) and the Greater Toronto Area (GTA, 6.3 million persons) were used as control and reference populations, respectively, for Oakville (160,000 persons). We compared sulfur dioxide and age- and season-standardized hospitalizations, considering potential factors such as changes in demographics, socio-economics, drug prescriptions, and environmental variables. Results: The closure of the refinery eliminated 6000 tons/year of SO(2) emissions, with an observed reduction of 20% in wind direction-adjusted ambient concentrations in Oakville. After accounting for trends, a decrease in cold-season peak-centered respiratory hospitalizations was observed for Oakville (reduction of 2.2 cases/1000 persons per year, [Formula: see text]) but not in Toronto (p = 0.856) and the GTA (p = 0.334). The reduction of respiratory hospitalizations in Oakville post closure appeared to have no observed link to known confounders or effect modifiers. Conclusion: The refinery closure allowed an assessment of the change in community health. This natural experiment provides evidence that a reduction in emissions was associated with improvements in population health. This study design addresses the impact of a removed source of air pollution.


title: Modifications of emergency dental clinic protocols to combat COVID‐19 transmission

text: During the COVID‐19 pandemic, incidence rates for dental diseases will continue unabated. However, the intent to prevent the spread of this lethal respiratory disease will likely lead to reduced treatment access due to restrictions on population movements. These changes have the potential to increase dental‐related emergency department visits and subsequently contribute to greater viral transmission. Moreover, dentists experience unique challenges with preventing transmission due to frequent aerosol‐producing procedures. This paper presents reviews and protocols implemented by directors and residents at the Dental College of Georgia to manage a dental emergency clinic during the COVID‐19 pandemic. The methods presented include committee‐based prioritization of dental patients, a multilayered screening process, team rotations with social and temporal spacing, and modified treatment room protocols. These efforts aid in the reduction of viral transmission, conservation of personal protective equipment, and expand provider availability. These protocols transcend a university and hospital‐based models and are applicable to private and corporate models.


title: The ProTides Boom

text: The masking of nucleoside phosphate and phosphonate groups by an aryl motif and an amino acid ester, nowadays known as the ‘ProTide’ technology, has proven to be effective in the discovery of nucleotide therapeutics. Indeed, this technology, which was invented by Chris McGuigan in the early 1990s, has inspired the discovery of two FDA‐approved antiviral nucleotide drugs, and many more are currently undergoing (pre)clinical development. The usefulness of this technology in the discovery of nucleotide therapeutics is showcased in this Highlight by discussing the ProTides development and the various ProTides that have reached clinical trials.


SARS‐CoV‐2 containment in complex surgical units during the COVID‐19 pandemic


title: Predictive Data Mining Models for Novel Coronavirus (COVID-19) Infected Patients’ Recovery

text: Novel coronavirus (COVID-19 or 2019-nCoV) pandemic has neither clinically proven vaccine nor drugs; however, its patients are recovering with the aid of antibiotic medications, anti-viral drugs, and chloroquine as well as vitamin C supplementation. It is now evident that the world needs a speedy and quicker solution to contain and tackle the further spread of COVID-19 across the world with the aid of non-clinical approaches such as data mining approaches, augmented intelligence and other artificial intelligence techniques so as to mitigate the huge burden on the healthcare system while providing the best possible means for patients' diagnosis and prognosis of the 2019-nCoV pandemic effectively. In this study, data mining models were developed for the prediction of COVID-19 infected patients’ recovery using epidemiological dataset of COVID-19 patients of South Korea. The decision tree, support vector machine, naive Bayes, logistic regression, random forest, and K-nearest neighbor algorithms were applied directly on the dataset using python programming language to develop the models. The model predicted a minimum and maximum number of days for COVID-19 patients to recover from the virus, the age group of patients who are of high risk not to recover from the COVID-19 pandemic, those who are likely to recover and those who might be likely to recover quickly from COVID-19 pandemic. The results of the present study have shown that the model developed with decision tree data mining algorithm is more efficient to predict the possibility of recovery of the infected patients from COVID-19 pandemic with the overall accuracy of 99.85% which stands to be the best model developed among the models developed with other algorithms including support vector machine, naive Bayes, logistic regression, random forest, and K-nearest neighbor.


title: Legal Issues in Quarantine and Isolation for Control of Emerging Infectious Diseases

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 has drawn public attention regarding the legal regulation of infectious disease control in Korea. This paper discusses the interpretive and legislative concerns regarding the Infectious Disease Prevention and Control Act, its ordinance and enforcement regulations, as well as public statements from the relevant administrative agency. Future improvements are also proposed.


title: CHAPTER 2 Infections, Inflammogens, and Drugs

text: Publisher Summary This chapter examines environmental inflammatory factors in vascular disease and dementia with a focus on infections, environmental inflammogens, and drugs that modulate both vascular disease and dementia. Infections and blood levels of inflammatory proteins are risk factors for future coronary events and possibly for dementia. When early age mortality is high, the survivors carry long-term infections that impair growth and accelerate mortality at later ages (“cohort morbidity phenotype”). Chronic infections, which are endured by most of the world's human and animal populations, cause energy reallocation for host defense. Infections and inflammation may impair stem cell generation, with consequences to arterial and brain aging. Diet may introduce glycotoxins that stimulate inflammation. Some anti-inflammatory and anti-coagulant drugs may protect against coronary artery disease and certain cancers, and possibly also for Alzheimer disease. These “pharmacopleiotropies” implicate shared mechanisms in diverse diseases of aging.


title: Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions

text: Abstract The coronavirus disease-19 pandemic (COVID-19), which appeared in China in December 2019 and rapidly spread throughout the world, has forced clinicians and scientists to take up extraordinary challenges. This unprecedented situation led to the inception of numerous fundamental research protocols and many clinical trials. It quickly became apparent that although COVID-19, in the vast majority of cases, was a benign disease, it could also develop a severe form with sometimes fatal outcomes. Cytokines are central to the pathophysiology of COVID-19; while some of them are beneficial (type-I interferon, interleukin-7), others appear detrimental (interleukin-1β, -6, and TNF-α) particularly in the context of the so-called cytokine storm. Yet another characteristic of the disease has emerged: concomitant immunodeficiency, notably involving impaired type-I interferon response, and lymphopenia. This review provides an overview of current knowledge on COVID-19 immunopathology. We discuss the defective type-I IFN response, the theoretical role of IL-7 to restore lymphocyte repertoire, as well as we mention the two patterns observed in severe COVID-19 (i.e. interleukin-1β-driven macrophage activation syndrome vs. interleukin-6-driven immune dysregulation). Next, reviewing current evidence drawn from clinical trials, we examine a number of cytokine and anti-cytokine therapies, including interleukin-1, -6, and TNF inhibitors, as well as less targeted therapies, such as corticosteroids, chloroquine, or JAK inhibitors.


title: Two Detailed Plaque Assay Protocols for the Quantification of Infectious SARS‐CoV‐2

text: Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) has been identified as the causal agent of COronaVIrus Disease‐19 (COVID‐19), an atypical pneumonia‐like syndrome that emerged in December 2019. While SARS‐CoV‐2 titers can be measured by detection of viral nucleic acid, this method is unable to quantitate infectious virions. Measurement of infectious SARS‐CoV‐2 can be achieved by tissue culture infectious dose−50 (TCID(50)), which detects the presence or absence of cytopathic effect in cells infected with serial dilutions of a virus specimen. However, this method only provides a qualitative infectious virus titer. Plaque assays are a quantitative method of measuring infectious SARS‐CoV‐2 by quantifying the plaques formed in cell culture upon infection with serial dilutions of a virus specimen. As such, plaque assays remain the gold standard in quantifying concentrations of replication‐competent lytic virions. Here, we describe two detailed plaque assay protocols to quantify infectious SARS‐CoV‐2 using different overlay and staining methods. Both methods have several advantages and disadvantages, which can be considered when choosing the procedure best suited for each laboratory. These assays can be used for several research purposes, including titration of virus stocks produced from infected cell supernatant and, with further optimization, quantification of SARS‐CoV‐2 in specimens collected from infected animals. © 2019 The Authors. Basic Protocol: SARS‐CoV‐2 plaque assay using a solid double overlay method Alternate Protocol: SARS‐CoV‐2 plaque assay using a liquid overlay and fixation‐staining method


Clinical feedback from experience with COVID-19: specific considerations for ExtraCorporeal Membrane Oxygenation


VR systems in dental education


title: Impact of the COVID-19 Pandemic on Neurosurgical Practice at an Academic Tertiary Referral Center: A Comparative Study

text: Abstract Background Neurosurgical services are affected by the COVID-19 pandemic, and several departments reported their experiences and responses to the COVID-19 crisis in an attempt to provide insights from which other impacted departments can benefit. Objective The goals of this study are to report the load and variety of emergent/urgent neurosurgical cases after implementing the ‘Battle Plan’ at an academic tertiary referral center during the COVID-19 pandemic and to compare these variables to previous practice at the same institution. Methods The clinical data of all patients who underwent a neurosurgical intervention between March 23, 2020 and April 20, 2020 was obtained from a prospectively maintained database. Data of the control group was retrospectively collected from the medical records to compare the types of surgeries/interventions performed by the same neurosurgical service before the COVID-19 pandemic started. Results Ninety-one patients underwent emergent, urgent and essential neurosurgical interventions over a 4-week period during the COVID-19 pandemic. Patient screening at teleclinics identified 11 urgent surgical cases. The implementation of the ‘Battle Plan’ led to a significant decrease in the case load, and the variation of cases by subspecialty is evident when compared to a control group comprised of 214 patients. Conclusion Delivery of optimal care and safe practice and education at an academic neurosurgical department can be well maintained with proper execution of crisis protocols. Teleclinics proved to be efficient in screening patients for urgent neurosurgical conditions, but in-person clinic visits may still be necessary for some cases in the immediate postoperative period.


title: COVID-19 and therapeutic drugs repurposing in hand: the need for collaborative efforts

text: Abstract The novel pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible to cause coronavirus disease-2019 (COVID-19). It is a global pandemic disease and has reached a new dimension with a higher death ratio. On 2 June 2020, World Health Organization (WHO) data showed more than 6,194,500 confirmed and 376,300 deaths globally due to the COVID-19. There are currently no approved medications or vaccines which have been claimed to be effective in COVID-19 prevention or treatment. Drug repurposing of available drugs and research studies for the search of new therapeutic agents are underway in various countries to try different combinations to treat their patients. It is too early to be sure of them as safe treatments because some reports seem to suggest some alarming side effects. However, a lot of work needs to be done to achieve a successful treatment result and the full safety and efficacy of the trial drugs will take some time to be developed. In this narrative perspective review, we addressed evidence-based literature on various possible antiviral medications, plant-derived antivirals drugs, and other valuable treatment options for COVID-19 management.


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title: Modeling the impact of non-pharmaceutical interventions on the dynamics of novel coronavirus with optimal control analysis with a case study

text: Coronavirus disease (COVID-19) is the biggest public health challenge the world is facing in recent days. Since there is no effective vaccine and treatment for this virus, therefore, the only way to mitigate this infection is the implementation of non-pharmaceutical interventions such as social-distancing, community lockdown, quarantine, hospitalization or self-isolation and contact-tracing. In this paper, we develop a mathematical model to explore the transmission dynamics and possible control of the COVID-19 pandemic in Pakistan, one of the Asian countries with a high burden of disease with more than 100,000 confirmed infected cases so far. Initially, a mathematical model without optimal control is formulated and some of the basic necessary analysis of the model, including stability results of the disease-free equilibrium is presented. It is found that the model is stable around the disease-free equilibrium both locally and globally when the basic reproduction number is less than unity. Despite the basic analysis of the model, we further consider the confirmed infected COVID-19 cases documented in Pakistan from March 1 till May 28, 2020 and estimate the model parameters using the least square fitting tools from statistics and probability theory. The results show that the model output is in good agreement with the reported COVID-19 infected cases. The approximate value of the basic reproductive number based on the estimated parameters is [Formula: see text]. The effect of low (or mild), moderate, and comparatively strict control interventions like social-distancing, quarantine rate, (or contact-tracing of suspected people) and hospitalization (or self-isolation) of testing positive COVID-19 cases are shown graphically. It is observed that the most effective strategy to minimize the disease burden is the implementation of maintaining a strict social-distancing and contact-tracing to quarantine the exposed people. Furthermore, we carried out the global sensitivity analysis of the most crucial parameter known as the basic reproduction number using the Latin Hypercube Sampling (LHS) and the partial rank correlation coefficient (PRCC) techniques. The proposed model is then reformulated by adding the time-dependent control variables u(1)(t) for quarantine and u(2)(t) for the hospitalization interventions and present the necessary optimality conditions using the optimal control theory and Pontryagin’s maximum principle. Finally, the impact of constant and optimal control interventions on infected individuals is compared graphically.


title: Recommendations of individualized medical treatment and common adverse events management for lung cancer patients during the outbreak of COVID‐19 epidemic

text: Since its outbreak in December 2019 in China, the novel coronavirus disease (COVID‐19) has rapidly spread and affected several countries. It has resulted in a difficult situation for cancer patients owing to the risks of the epidemic situation outbreak as well as cancer. Patients with cancer are more likely than the general population to contract COVID‐19 because of the systemic immunosuppressive status caused by malignant diseases or anticancer treatment. Lung cancer has the highest morbidity and mortality in China and the world. Most patients with lung cancer are smokers with poor underlying lung conditions and low immunity, thus it is vital to protect them from epidemic diseases during cancer treatment. It is necessary to provide individualized medical treatment and management of treatment‐related adverse events for patients with lung cancer based on patients' conditions and regional epidemic patterns.


Slaughterhouses: A major target for COVID-19 prevention


title: A new membrane based process to isolate immunoglobulin from chicken egg yolk

text: Abstract Although the importance of eggs as a source of specific antibodies has been well recognised, the generation of egg yolk immunoglobulins (IgY) is rarely chosen due to the peculiar composition of egg yolk and the lack of specific affinity ligands. In this work, we report a novel membrane based two-stage ultrafiltration process to isolate IgY from egg yolk. The effects of solution pH, ionic strength, stirring speed and permeate flux on the transmission of proteins were quantified using the pulsed sample injection technique and parameter scanning ultrafiltration. Under optimised conditions, the purity of immunoglobulin obtained was greater than 93% after the two-stage ultrafiltration process and the recovery of immunoglobulin from the feedstock was close to 87%. The resulting immunoglobulin product was then analysed by Isoelectric Focusing (IEF), SDS–PAGE and Circular Dichroism (CD), to confirm its isoelectric point, molecular weight and molecular secondary structure.


title: Knowledge and beliefs towards universal safety precautions during the coronavirus disease (COVID-19) pandemic among the Indian public: a web-based cross-sectional survey

text: BACKGROUND: The novel coronavirus disease 2019 (COVID-19) is considered the most serious global health threat in recent times. As there is a current lack of approved treatments and vaccines, universal safety precautions (USPs) must be taken to deal with this emergency. OBJECTIVE: The aim of this study was to assess the knowledge and beliefs of the Indian public with regard to USPs during the COVID-19 pandemic. METHODS: A cross-sectional, web-based survey was conducted during March 2020. A 20-item self-administered questionnaire was developed, validated and distributed using Google Forms through social media networks. Binary logistic regression analysis was used to identify the factors influencing knowledge regarding COVID-19 USPs. RESULTS: Of the 1117 individuals who participated in the survey, the mean age was 28.8 ± 10.9 years, 32.9% had a post-graduate education, 45% had a professional job, and 40% belonged to the upper-middle economic class. Overall, the mean correct response scores were 63% for USP knowledge and 83% for USP beliefs. All the sociodemographic variables were significantly (p < 0.001) associated with the USP knowledge levels. Importantly, students were less likely to have a lower level of USP knowledge compared with the other occupations (odds ratio 0.35, 95% CI 0.23–0.53; p < 0.001). CONCLUSION: Although the knowledge and beliefs of the Indian public towards USPs are encouraging, there is a need for long-term educational interventions as the dynamics and severity of COVID-19 rapidly change. These findings could guide public health authorities to make and implement precautionary measures to combat this pandemic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40267-020-00752-8) contains supplementary material, which is available to authorized users.


title: The Phylogeography of MERS-CoV in Hospital Outbreak-Associated Cases Compared to Sporadic Cases in Saudi Arabia

text: This study compared the phylogeography of MERS-CoV between hospital outbreak-associated cases and sporadic cases in Saudi Arabia. We collected complete genome sequences from human samples in Saudi Arabia and data on the multiple risk factors of human MERS-CoV in Saudi Arabia reported from 2012 to 2018. By matching each sequence to human cases, we identified isolates as hospital outbreak-associated cases or sporadic cases. We used Bayesian phylogenetic methods including temporal, discrete trait analysis and phylogeography to uncover transmission routes of MERS-CoV isolates between hospital outbreaks and sporadic cases. Of the 120 sequences collected between 19 June 2012 and 23 January 2017, there were 64 isolates from hospital outbreak-associated cases and 56 from sporadic cases. Overall, MERS-CoV is fast evolving at 7.43 × 10(−4) substitutions per site per year. Isolates from hospital outbreaks showed unusually fast evolutionary speed in a shorter time-frame than sporadic cases. Multiple introductions of different MERS-CoV strains occurred in three separate hospital outbreaks. MERS-CoV appears to be mutating in humans. The impact of mutations on viruses transmissibility in humans is unknown.


title: Chapter 5 Upper Airway Infections

text: Abstract Infections of the upper respiratory tract represent an important source of morbidity and potentially of life-threatening complications. This group of infections represents one of the most frequent outpatient consultations; and includes a range of clinical syndromes that may go from a self-limited common cold, to acute rhinosinusitis, otitis media, to life threatening condition such as epiglottitis. Importantly, acute respiratory illness account for approximately 75% of the total number of antibiotic prescriptions per year; an often many of these conditions are of viral origin. When acute pharyngitis is caused by Streptococcus pyogenes, it is important to consider treatment to prevent transmission, reduce symptoms, and prevent its associated suppurative and nonsuppurative complications. Acute bacterial sinusitis can be associated with severe complications. Upper respiratory infection can also lead to life-threatening infections of the peripharyngeal and deep fascial spaces of the head and neck.


title: Chapter 14 Biosecurity Strategies for Backyard Poultry: A Controlled Way for Safe Food Production

text: Abstract The people of rural and periurban India depend on backyard farming system for poultry meat and eggs. It is used by weaker sections of society, such as marginal farmers as insurance against crop failure, for ready cash and to ensure basic economic returns and the empowerment of women and children. However, backyard farming does not appear to be a promising strategy to achieve the poverty reduction until the production level is increased. The major constraint in increasing the production in backyard birds is microbial infection due to lack of biosecurity knowledge among the farmers. The mitigation of the microbial infection depends on the detection of the infection route and its prevention. The source of microbial infection (Salmonella, Escherichia coli) and their dissemination through the eggs in backyard flocks kept in different agroclimatic zones of West Bengal, a major egg producing state in India, was identified. The pattern of virulence gene specially associated with urinary tract infection and antibiotic resistance genes, such as extended spectrum β lactamase (ESBL) genes of the isolates was studied. The chapter will elaborate the backyard farming including breeds reared, housing, feeding with special emphasis on suggested biosecurity strategies and consequence of the adapted strategy.