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j3ucvetz
Competition law in times of crisis—tackling the COVID-19 challenge
w2m3cqlx
CoVID-19 vs. epilepsy: It is time to move, act and encourage physical exercise’?
fu02qqsh
Virus-Vectored Ebola Vaccines
The Ebola virus disease (EVD) is one of the most dangerous infections affecting humans and animals. The first EVD outbreaks occurred in 1976 in Sudan and Zaire. Since then, more than 20 outbreaks have occurred; the largest of which (2014−2016) evolved into an epidemic in West Africa and claimed the lives of more than 11,000 people. Although vaccination is the most effective way to prevent epidemics, there was no licensed vaccine for EVD at the beginning of the latest outbreak. The development of the first vaccines for EVD started in 1980 and has come a long technological way, from inactivated to genetically engineered vaccines based on recombinant viral vectors. This review focuses on virus-vectored Ebola vaccines that have demonstrated the greatest efficacy in preclinical trials and are currently under different phases of clinical trial. Particular attention is paid to the mechanisms of immune response development, which are important for protection from EVD, and the key vaccine parameters necessary for inducing long-term protective immunity against EVD.
covnpc8z
A novel coronavirus capable of lethal human infections: an emerging picture
SUMMARY: In September 2012, a novel coronavirus was isolated from a patient in Saudi Arabia who had died of an acute respiratory illness and renal failure. The clinical presentation was reminiscent of the outbreak caused by the SARS-coronavirus (SARS-CoV) exactly ten years ago that resulted in over 8000 cases. Sequence analysis of the new virus revealed that it was indeed a member of the same genus as SARS-CoV. By mid-February 2013, 12 laboratory-confirmed cases had been reported with 6 fatalities. The first 9 cases were in individuals resident in the Middle East, while the most recent 3 cases were in family members resident in the UK. The index case in the UK family cluster had travel history to Pakistan and Saudi Arabia. Although the current evidence suggests that this virus is not highly transmissible among humans, there is a real danger that it may spread to other parts of the world. Here, a brief review of the events is provided to summarize the rapidly emerging picture of this new virus.
xbsvofir
The threat of climate change to non-dengue-endemic countries: increasing risk of dengue transmission potential using climate and non-climate datasets
BACKGROUND: Dengue is a major public health problem in the tropics and sub-tropics, but the disease is less known to non-dengue-endemic countries including in Northeast Asia. However, an unexpected dengue outbreak occurred in 2014 in Japan. Given that autochthonous (domestic) dengue cases had not been reported for the past 70 years in Japan, this outbreak was highly unusual and suggests that several environmental factors might have changed in a way that favors vector mosquitoes in the Northeast Asian region. METHODS: A Climate Risk Factor (CRF) index, as validated in previous work, was constructed using climate and non-climate factors. This CRF index was compared to the number of reported dengue cases in Tokyo, Japan where the outbreak was observed in 2014. In order to identify high-risk areas, the CRF index was further estimated at the 5 km by 5 km resolution and mapped for Japan and South Korea. RESULTS: The high-risk areas determined by the CRF index corresponded well to the provinces where a high number of autochthonous cases were reported during the outbreak in Japan. At the provincial-level, high-risk areas for dengue fever were the Eastern part of Tokyo and Kanakawa, the South-Eastern part of Saitama, and the North-Western part of Chiba. While a relatively small number of high-risk areas were identified in South Korea compared with Japan, the high-risk areas in South Korea include popular tourist destinations where international visitors have been increasing. CONCLUSION: The recent dengue outbreak in Japan may signal that the two adjacent non-dengue-endemic countries are also exposed to the risk of temporal and sporadic behavior of dengue fever. It is critical to understand potential high-risk areas for future outbreaks and to set up appropriate prevention activities at the governmental-level.
lipme817
Neuropsychiatric Symptoms in an Adolescent Boy with Multisystem Inflammatory Syndrome in Children (MIS-C)
BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) related to coronavirus disease-2019 (COVID-19) is an emergent syndrome affecting children globally in the wake of the SARS-CoV-2 pandemic. The clinical presentation has similarities to Kawasaki disease and toxic shock syndrome. As knowledge of the cardiac and gastrointestinal manifestations has been emerging, little is known about the impact on the brain. METHOD: This case describes a 14-year-old boy who developed prominent neuropsychiatric symptoms including delirium followed by impairments in executive functioning in the context of MIS-C with positive SARS-CoV-2 antibodies. These symptoms improved in correlation with improvements in inflammatory markers. RESULTS: Neuropsychiatric manifestations including confusion, irritability, and headaches have been reported in pediatric patients with MIS-C. Potential mechanisms include direct neurotropic effect of SARS-CoV-2, secondary effects of systemic inflammation, and/or adverse side effects of treatment. CONCLUSIONS: MIS-C is a novel and poorly understood syndrome related to SARS-CoV-2 with effects on multiple organ systems including the central nervous system. As additional cases are reported and research expands, so too will our understanding of the neuropsychiatric manifestations. Better understanding of the underlying pathophysiology would aid in determining targeted interventions.
50wccmhi
Prevalence of antibodies against COVID-19 in the staff of a COVID-19 regular ward
pkniwunl
“The storm has arrived”: the impact of SARS-CoV-2 on medical students
In a few weeks, the global community has witnessed, and for some of us experienced first-hand, the human costs of the COVID-19 pandemic. There is incredible variability in how countries are choosing to thwart the disease’s outbreak, sparking intense discussions around what it means to teach and learn in the era of COVID-19, and more specifically, the role medical students play in the midst of the pandemic. A multi-national and multi-institutional group made up of a dedicated medical student from Austria, passionate clinicians and educators from Switzerland, and a PhD scientist involved in Medical Education from Canada, have assembled to summarize the ingenious ways medical students around the world are contributing to emergency efforts. They argue that such efforts change COVID-19 from a “disruption” to medical students learning to something more tangible, more important, allowing students to become stakeholders in the expansion and delivery of healthcare.
tkdh740c
Giant Reverse Transcriptase-Encoding Transposable Elements at Telomeres
Transposable elements are omnipresent in eukaryotic genomes and have a profound impact on chromosome structure, function and evolution. Their structural and functional diversity is thought to be reasonably well-understood, especially in retroelements, which transpose via an RNA intermediate copied into cDNA by the element-encoded reverse transcriptase, and are characterized by a compact structure. Here, we report a novel type of expandable eukaryotic retroelements, which we call Terminons. These elements can attach to G-rich telomeric repeat overhangs at the chromosome ends, in a process apparently facilitated by complementary C-rich repeats at the 3′-end of the RNA template immediately adjacent to a hammerhead ribozyme motif. Terminon units, which can exceed 40 kb in length, display an unusually complex and diverse structure, and can form very long chains, with host genes often captured between units. As the principal polymerizing component, Terminons contain Athena reverse transcriptases previously described in bdelloid rotifers and belonging to the enigmatic group of Penelope-like elements, but can additionally accumulate multiple cooriented ORFs, including DEDDy 3′-exonucleases, GDSL esterases/lipases, GIY-YIG-like endonucleases, rolling-circle replication initiator (Rep) proteins, and putatively structural ORFs with coiled-coil motifs and transmembrane domains. The extraordinary length and complexity of Terminons and the high degree of interfamily variability in their ORF content challenge the current views on the structural organization of eukaryotic retroelements, and highlight their possible connections with the viral world and the implications for the elevated frequency of gene transfer.
9pz3phtd
Difficulty of downscaling the precautions for coronavirus disease-19 based on negative throat polymerase chain results in the early phase of infection
Abstract We here report a case of coronavirus disease-19 (COVID-19) in Japan in which the initial throat swab polymerase chain reaction result was negative The possibility of false-negative results in the early phase of disease suggest reconsideration of the feasibility of a community or national infection control framework to prevent transmission. We recommend establishing an alternative feasible system, such as self-isolation by contact history in non-endemic community and by symptoms in endemic community, not relying on the PCR examination, to minimize this ongoing COVID-19 outbreak. Further rapid accumulation of knowledge including incubation period, clinical course and types of transmission is warranted to control this outbreak.
mlshkaid
COVID-19: Lessons for an Urban(izing) World
The COVID-19 crisis has changed the face of many of our cities and questioned how we should manage urban life in the wake of a pandemic. This Commentary points to the need to learn urban governance lessons and to the potential value of urban experimentation in crisis.
602a2xdn
Coronavirus Genomics and Bioinformatics Analysis
The drastic increase in the number of coronaviruses discovered and coronavirus genomes being sequenced have given us an unprecedented opportunity to perform genomics and bioinformatics analysis on this family of viruses. Coronaviruses possess the largest genomes (26.4 to 31.7 kb) among all known RNA viruses, with G + C contents varying from 32% to 43%. Variable numbers of small ORFs are present between the various conserved genes (ORF1ab, spike, envelope, membrane and nucleocapsid) and downstream to nucleocapsid gene in different coronavirus lineages. Phylogenetically, three genera, Alphacoronavirus, Betacoronavirus and Gammacoronavirus, with Betacoronavirus consisting of subgroups A, B, C and D, exist. A fourth genus, Deltacoronavirus, which includes bulbul coronavirus HKU11, thrush coronavirus HKU12 and munia coronavirus HKU13, is emerging. Molecular clock analysis using various gene loci revealed that the time of most recent common ancestor of human/civet SARS related coronavirus to be 1999–2002, with estimated substitution rate of 4×10(−4) to 2×10(−2) substitutions per site per year. Recombination in coronaviruses was most notable between different strains of murine hepatitis virus (MHV), between different strains of infectious bronchitis virus, between MHV and bovine coronavirus, between feline coronavirus (FCoV) type I and canine coronavirus generating FCoV type II, and between the three genotypes of human coronavirus HKU1 (HCoV-HKU1). Codon usage bias in coronaviruses were observed, with HCoV-HKU1 showing the most extreme bias, and cytosine deamination and selection of CpG suppressed clones are the two major independent biological forces that shape such codon usage bias in coronaviruses.
24gp0tno
Just-in-Time Simulation to Guide Workflow Design for Coronavirus Disease 2019 Difficult Airway Management
OBJECTIVES: The coronavirus disease 2019 pandemic has required that hospitals rapidly adapt workflows and processes to limit disease spread and optimize the care of critically ill children. DESIGN AND SETTING: As part of our institution’s coronavirus disease 2019 critical care workflow design process, we developed and conducted a number of simulation exercises, increasing in complexity, progressing to intubation wearing personal protective equipment, and culminating in activation of our difficult airway team for an airway emergency. PATIENTS AND INTERVENTIONS: In situ simulations were used to identify and rework potential failure points to generate guidance for optimal airway management in coronavirus disease 2019 suspected or positive children. Subsequent to this high-realism difficult airway simulation was a real-life difficult airway event in a patient suspected of coronavirus disease 2019 less than 12 hours later, validating potential failure points and effectiveness of rapidly generated guidance. MEASUREMENTS AND MAIN RESULTS: A number of potential workflow challenges were identified during tabletop and physical in situ manikin-based simulations. Experienced clinicians served as participants, debriefed, and provided feedback that was incorporated into local site clinical pathways, job aids, and suggested practices. Clinical management of an actual suspected coronavirus disease 2019 patient with difficult airway demonstrated very similar success and anticipated failure points. Following debriefing and assembly of a success/failure grid, a coronavirus disease 2019 airway bundle template was created using these simulations and clinical experiences for others to adapt to their sites. CONCLUSIONS: Integration of tabletop planning, in situ simulations, and debriefing of real coronavirus disease 2019 cases can enhance planning, training, job aids, and feasible policies/procedures that address human factors, team communication, equipment choice, and patient/provider safety in the coronavirus disease 2019 pandemic era.
u5z5cpfk
Atypical Neurological Manifestations of COVID-19
The novel coronavirus (SARS-CoV-2), belonging to a group of RNA-enveloped viruses and believed to be transmitted by aerosol route, is a worldwide pandemic. Many studies have described typical clinical manifestations such as fever, cough, fatigue, diarrhea, and nasal congestion. However, to our knowledge, there are minimal studies on the neurological manifestations in SARS-CoV-2 positive patients. Our review aims to identify the various neurological manifestations in SARS-CoV-2 positive patients, which could be an added advantage in the early diagnosis and prevention of further complications of the nervous system.
b5s67twk
Semi-quantitative visual assessment of chest radiography is associated with clinical outcomes in critically ill patients
BACKGROUND: Respiratory pathology is a major driver of mortality in the intensive care unit (ICU), even in the absence of a primary respiratory diagnosis. Prior work has demonstrated that a visual scoring system applied to chest radiographs (CXR) is associated with adverse outcomes in ICU patients with Acute Respiratory Distress Syndrome (ARDS). We hypothesized that a simple, semi-quantitative CXR score would be associated with clinical outcomes for the general ICU population, regardless of underlying diagnosis. METHODS: All individuals enrolled in the Registry of Critical Illness at Brigham and Women’s Hospital between June 2008 and August 2018 who had a CXR within 24 h of admission were included. Each patient’s CXR was assigned an opacification score of 0–4 in each of four quadrants with the total score being the sum of all four quadrants. Multivariable negative binomial, logistic, and Cox regression, adjusted for age, sex, race, immunosuppression, a history of chronic obstructive pulmonary disease, a history of congestive heart failure, and APACHE II scores, were used to assess the total score’s association with ICU length of stay (LOS), duration of mechanical ventilation, in-hospital mortality, 60-day mortality, and overall mortality, respectively. RESULTS: A total of 560 patients were included. Higher CXR scores were associated with increased mortality; for every one-point increase in score, in-hospital mortality increased 10% (OR 1.10, CI 1.05–1.16, p < 0.001) and 60-day mortality increased by 12% (OR 1.12, CI 1.07–1.17, p < 0.001). CXR scores were also independently associated with both ICU length of stay (rate ratio 1.06, CI 1.04–1.07, p < 0.001) and duration of mechanical ventilation (rate ratio 1.05, CI 1.02–1.07, p < 0.001). CONCLUSIONS: Higher values on a simple visual score of a patient’s CXR on admission to the medical ICU are associated with increased in-hospital mortality, 60-day mortality, overall mortality, length of ICU stay, and duration of mechanical ventilation.
415eod1f
Vox Sanguinis International Forum on Hospital Transfusion Services' Response to COVID‐19
The novel coronavirus (SARS‐Cov‐2) that was first reported in Wuhan, China and provokes the COVID‐19 disease has developed into a pandemic with hundreds of thousands of people infected. Many governments have enforced social isolation protocols on their citizens, which has led to the closure of many large public gatherings in order to limit the spread of the virus. These closures could reasonably be expected to affect blood collections, thereby presaging shortages of blood for transfusion. On the other hand, steps such as the postponement of elective surgeries and other non‐urgent transfusions could mitigate against potential shortfalls in the blood supply.
osgi06o4
Conjunctivitis as a Sentinel of SARS-CoV-2 Infection: a Need of Revision for Mild Symptoms
COVID-19 has been declared a pandemic by the World Health Organization on March 11, and since then, more than 3 million cases and a quarter million deaths have occurred due to it. Lately, there is a growing evidence for an ophthalmologic symptom (conjunctivitis) to be connected with the disease. This seems to happen in early stages of the infection by SARS-CoV-2, and thus, it is of major importance to understand the mechanism through which the virus can facilitate such a symptom. Here, we are proposing a molecular mechanism through which the novel coronavirus could act in order to affect the eye and use it as another, secondary but alternative, point of entry to the host organism.
m1jbpo5l
Human Bocavirus and Acute Wheezing in Children
Background. Human bocavirus is a newly discovered parvovirus. It has been detected primarily in children with acute lower respiratory tract infection, but its occurrence, clinical profile, and role as a causative agent of respiratory tract disease are not clear. Methods. We investigated the presence of human bocavirus by quantitative polymerase chain reaction of nasopharyngeal aspirate specimens and selected serum samples obtained from 259 children (median age, 1.6 years) who had been hospitalized for acute expiratory wheezing. The samples were analyzed for 16 respiratory viruses by polymerase chain reaction, virus culture, antigen detection, and serological assays. Results. At least 1 potential etiologic agent was detected in 95% of children, and >1 agent was detected in 34% of children. Human bocavirus was detected in 49 children (19%). A large proportion of the cases were mixed infections with other viruses, but human bocavirus was the only virus detected in 12 children (5%). High viral loads of human bocavirus were noted mainly in the absence of other viral agents, suggesting a causative role for acute wheezing. In addition, infections that had uncertain clinical relevance and low viral loads were prevalent. Human bocavirus DNA was frequently detected in serum specimens obtained from patients with acute wheezing, suggesting systemic infection. Conclusions. Human bocavirus is prevalent among children with acute wheezing and can cause systemic infection. Results suggest a model for bocavirus infection in which high viral loads are potentially associated with respiratory symptoms and low viral loads indicate asymptomatic shedding. Therefore, quantitative polymerase chain reaction analysis may be important for additional studies of human bocavirus.
q82gkygd
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Induced Cardiovascular Syndrome: Etiology, Outcomes, and Management
As the coronavirus disease 2019 (COVID-19) pandemic evolves, more complications associated with the disease come to surface. Thus far, there is limited information available on the etiology, clinical outcomes, and management options for cardiovascular complications caused by COVID-19. This review focuses on literature published in year 2020 on the virus-induced cardiovascular damage with intention to better understand pathophysiology of this process, its impact on clinical outcomes, and available therapies. Literature review shows that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) acts through angiotensin-converting enzyme 2 (ACE-2) receptors and causes cardiac injury by direct damage to the cardiomyocytes, systemic inflammation, fibrosis, interferon and cytokine-mediated immune response, coronary plaque destabilization, and hypoxia. Comorbidities, especially underling heart disease, make patients more predisposed to severe cardiovascular damage. COVID-19 patients who develop myocardial injury have a higher mortality rate compared to those who do not. During the pandemic, percutaneous coronary intervention (PCI) should remain the standard of care for patients with ST segment elevation myocardial infarction (STEMI). On the other hand, in order to limit healthcare worker exposure, patients with non-ST segment elevation myocardial infarction (NSTEMI) should be managed with stabilization strategies if hemodynamically stable. Monitoring hospitalized COVID-19 patients with high sensitivity troponin can help screen for severe complications and detect them early. Use of multiple investigational drugs with uncertain cardiac safety profiles in COVID-19 patients requires continuous cardiac monitoring. Notch signaling pathway therapy along with anti-viral agents, interleukin-6 inhibitors, and convalescent serum are possible treatment options to better control the inflammatory state that drives the cardiac damage.
mqv7106v
COVID‐19 infection in solid organ transplant recipients: A single‐center experience with patients immediately after transplantation
In our transplant center, infection with SARS‐CoV‐2 virus was confirmed in 4 organ transplant recipients (3 kidney and 1 liver transplant recipients) during their early post‐transplant hospital stay. In this paper, we report the basic characteristics, management, clinical course, and outcomes of these patients.
4dk7mkut
Rapid diagnosis of gastrointestinal tract infections due to parasites, viruses, and bacteria
Abstract Rapid diagnostic techniques are valuable tools in the diagnosis of gastrointestinal infections, especially for the detection of some microorganisms and in certain groups of patients. While antigen detection techniques are widely used in Clinical Microbiology laboratories, for the diagnosis of viruses, some parasites and some bacteria, molecular techniques are routinely used only for some pathogens (such as Clostridium difficile). However, molecular techniques are constantly evolving, and they allow a rapid diagnosis for an increasing number of pathogens, with high sensitivity and specificity. In addition, they are also able to detect virulence factors or resistance mechanisms. Syndromic surveillance systems, which detect different pathogens simultaneously, are very promising because they enable the most frequent pathogens to be diagnosed in a few hours and they can be very useful in certain patients. For the diagnosis of Helicobacter pylori infection, molecular techniques are able to detect bacteria and its resistance to clarithromycin and levofloxacin, allowing the most appropriate treatment to be selected for each patient when bacterial culture is not possible.
4al2c1qe
Sleep problems among Chinese adolescents and young adults during the coronavirus-2019 pandemic
OBJECTIVE: To assess the prevalence and sociodemographic correlates of insomnia symptoms among Chinese adolescents and young adults affected by the outbreak of coronavirus disease-2019 (COVID-19). METHODS: This cross-sectional study included Chinese adolescents and young adults 12–29 years of age during part of the COVID-19 epidemic period. An online survey was used to collect demographic data, and to assess recognition of COVID-19, insomnia, depression, and anxiety symptoms using the Pittsburgh Sleep Quality Index (PSQI), the Patient Health Questionnaire (PHQ-9), and the Generalized Anxiety Disorder (GAD-7) questionnaires, respectively. The Social Support Rate Scale was used to assess social support. RESULTS: Among 11,835 adolescents and young adults included in the study, the prevalence of insomnia symptoms during part of the COVID-19 epidemic period was 23.2%. Binomial logistic regression analysis revealed that female sex and residing in the city were greater risk factors for insomnia symptoms. Depression or anxiety were risk factors for insomnia symptoms; however, social support, both subjective and objective, was protective factors against insomnia symptoms. Furthermore, anxiety and depression symptoms were mediators of social support and insomnia symptoms. CONCLUSIONS: Results of this study revealed a high prevalence of sleep problems among adolescents and young adults during the COVID-19 epidemic, especially senior high school and college students, which were negatively associated with students’ projections of trends in COVID-19. The adverse impact of COVID-19 was a risk factor for insomnia symptoms; as such, the government must devote more attention to sleep disorders in this patient population while combating COVID-19.
5j4oz8ds
Zooming in to Westminster
One of BVA's key roles is informing parliamentarians about the issues affecting the veterinary profession and lobbying directly on behalf of members. In early June we organised a virtual Westminster briefing for MPs and Peers to bring them up to date with the impact of Covid-19 on vets across the UK.
3stjueja
COVID-19 kills at home: the close relationship between the epidemic and the increase of out-of-hospital cardiac arrests
AIMS: An increase in out-of-hospital cardiac arrest (OHCA) incidence has been reported in the very early phase of the COVID-19 epidemic, but a clear demonstration of a correlation between the increased incidence of OHCA and COVID-19 is missing so far. We aimed to verify whether there is an association between the OHCA difference compared with 2019 and the COVID-19 epidemic curve. METHODS AND RESULTS: We included all the consecutive OHCAs which occurred in the Provinces of Lodi, Cremona, Pavia, and Mantova in the 2 months following the first documented case of COVID-19 in the Lombardia Region and compared them with those which occurred in the same time frame in 2019. The cumulative incidence of COVID-19 from 21 February to 20 April 2020 in the study territory was 956 COVID-19/100 000 inhabitants and the cumulative incidence of OHCA was 21 cases/100 000 inhabitants, with a 52% increase as compared with 2019 (490 OHCAs in 2020 vs. 321 in 2019). A strong and statistically significant correlation was found between the difference in cumulative incidence of OHCA between 2020 and 2019 per 100 000 inhabitants and the COVID-19 cumulative incidence per 100 000 inhabitants both for the overall territory (ρ 0.87, P < 0.001) and for each province separately (Lodi: ρ 0.98, P < 0.001; Cremona: ρ 0.98, P < 0.001; Pavia: ρ 0.87, P < 0.001; Mantova: ρ 0.81, P < 0.001). CONCLUSION: The increase in OHCAs in 2020 is significantly correlated to the COVID-19 pandemic and is coupled with a reduction in short-term outcome. Government and local health authorities should seriously consider our results when planning healthcare strategies to face the epidemic, especially considering the expected recurrent outbreaks.
55iqqzhy
The saga continues: is COVID-19 a cardiopulmonary disease?
dm7rx4ls
Genetic properties of endemic Chinese porcine epidemic diarrhea virus strains isolated since 2010
Acute diarrhea outbreaks caused by porcine epidemic diarrhea virus (PEDV) have been observed in various pig-breeding provinces of China since December 2010. Endemic strains of PEDV were isolated from different areas, and the complete genome sequences of 10 isolates were determined. Our objective in this study was to genetically characterize current Chinese field isolates of PEDV to better understand their epidemiology and genetic diversity. Sequence analysis showed that 10 post-2010 isolates shared high homology with each other and were always clustered together with the virulent DR13 strains (South Korea) and/or one earlier Chinese strain, CH-S, in phylogenetic analysis. All post-2010 isolates possessed common sequence changes in each gene. Our results suggest that current Chinese PEDV isolates originated from either South Korean and/or Chinese ancestors that underwent some genetic variation, thereby forming a new PEDV genotype in China.
dmb0293x
Recent Advances of Vaccine Adjuvants for Infectious Diseases
Vaccines are the most effective and cost-efficient method for preventing diseases caused by infectious pathogens. Despite the great success of vaccines, development of safe and strong vaccines is still required for emerging new pathogens, re-emerging old pathogens, and in order to improve the inadequate protection conferred by existing vaccines. One of the most important strategies for the development of effective new vaccines is the selection and usage of a suitable adjuvant. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Thus, formulation of vaccines with appropriate adjuvants is an attractive approach towards eliciting protective and long-lasting immunity in humans. However, only a limited number of adjuvants is licensed for human vaccines due to concerns about safety and toxicity. We summarize current knowledge about the potential benefits of adjuvants, the characteristics of adjuvants and the mechanisms of adjuvants in human vaccines. Adjuvants have diverse modes of action and should be selected for use on the basis of the type of immune response that is desired for a particular vaccine. Better understanding of current adjuvants will help exploring new adjuvant formulations and facilitate rational design of vaccines against infectious diseases.
69mf7wi7
Barriers to implementing antimicrobial stewardship programmes in three Saudi hospitals: Evidence from a qualitative study
Abstract Objectives This study explored antimicrobial stewardship programme (ASP) team members’ perspectives regarding factors influencing the adoption and implementation of these programmes in Saudi hospitals. Methods This was a qualitative study based on face-to-face semistructured interviews with healthcare professionals involved in ASPs and activities across three Ministry of Health (MoH) hospitals in Saudi Arabia (n = 18). Interviews were also conducted with two representatives of a General Directorate of Health Affairs in a Saudi region and two representatives of the Saudi MoH (n = 4) between January–February 2017. Results Despite the existence of a national strategy to implement ASPs in Saudi MoH hospitals, their adoption and implementation remains low. Hospitals have their own antimicrobial stewardship policies, but adherence to these is poor. ASP team members highlight that lack of enforcement of policies and guidelines from the MoH and hospital administration is a significant barrier to ASP adoption and implementation. Other barriers include disintegration of teams, poor communication, lack of recruitment/shortage of ASP team members, lack of education and training, and lack of health information technology (IT). Physicians’ fears and concerns in relation to liability are also a barrier to their adoption of ASPs. Conclusion This is the first qualitative study exploring barriers to ASP adoption and implementation in Saudi hospitals from the perspective of ASP team members. Formal endorsement of ASPs from the MoH as well as hospital enforcement of policies and provision of human and health IT resources would improve the adoption and implementation of ASPs in Saudi hospitals.
vczjb3v7
Safety and efficacy of amiodarone in a patient with COVID-19
Abstract There is an urgent need of effective treatments for COVID-19. Amiodarone, like hydroxychloroquine, exerts antiviral actions by interfering with endocytosis and viral replication. Here we report the first case of a patient affected by respiratory failure related to COVID-19, and recovering after only supportive measures and a short amiodarone course.
hf4d5zi4
Hepatitis B: Prevalence, Hope
yesxg84u
Anatomy of the Epidemiological Literature on the 2003 SARS Outbreaks in Hong Kong and Toronto: A Time-Stratified Review
BACKGROUND: Outbreaks of emerging infectious diseases, especially those of a global nature, require rapid epidemiological analysis and information dissemination. The final products of those activities usually comprise internal memoranda and briefs within public health authorities and original research published in peer-reviewed journals. Using the 2003 severe acute respiratory syndrome (SARS) epidemic as an example, we conducted a comprehensive time-stratified review of the published literature to describe the different types of epidemiological outputs. METHODS AND FINDINGS: We identified and analyzed all published articles on the epidemiology of the SARS outbreak in Hong Kong or Toronto. The analysis was stratified by study design, research domain, data collection, and analytical technique. We compared the SARS-case and matched-control non-SARS articles published according to the timeline of submission, acceptance, and publication. The impact factors of the publishing journals were examined according to the time of publication of SARS articles, and the numbers of citations received by SARS-case and matched-control articles submitted during and after the epidemic were compared. Descriptive, analytical, theoretical, and experimental epidemiology concerned, respectively, 54%, 30%, 11%, and 6% of the studies. Only 22% of the studies were submitted, 8% accepted, and 7% published during the epidemic. The submission-to-acceptance and acceptance-to-publication intervals of the SARS articles submitted during the epidemic period were significantly shorter than the corresponding intervals of matched-control non-SARS articles published in the same journal issues (p<0.001 and p<0.01, respectively). The differences of median submission-to-acceptance intervals and median acceptance-to-publication intervals between SARS articles and their corresponding control articles were 106.5 d (95% confidence interval [CI] 55.0–140.1) and 63.5 d (95% CI 18.0–94.1), respectively. The median numbers of citations of the SARS articles submitted during the epidemic and over the 2 y thereafter were 17 (interquartile range [IQR] 8.0–52.0) and 8 (IQR 3.2–21.8), respectively, significantly higher than the median numbers of control article citations (15, IQR 8.5–16.5, p<0.05, and 7, IQR 3.0–12.0, p<0.01, respectively). CONCLUSIONS: A majority of the epidemiological articles on SARS were submitted after the epidemic had ended, although the corresponding studies had relevance to public health authorities during the epidemic. To minimize the lag between research and the exigency of public health practice in the future, researchers should consider adopting common, predefined protocols and ready-to-use instruments to improve timeliness, and thus, relevance, in addition to standardizing comparability across studies. To facilitate information dissemination, journal managers should reengineer their fast-track channels, which should be adapted to the purpose of an emerging outbreak, taking into account the requirement of high standards of quality for scientific journals and competition with other online resources. Please see later in the article for the Editors' Summary
l2pfl776
A rebuttal to the comments on the genome order index and the Z-curve
BACKGROUND: Elhaik, Graur and Josic recently commented on the genome order index (S) and the Z-curve (Elhaik et al. Biol Direct 2010, 5: 10). S is a quantity defined as S = a(2 )+ c(2 )+ g(2 )+ t(2), where a, c, g and t denote corresponding base frequencies. The Z-curve is a three dimensional curve that represents a DNA sequence in the manner that each can be uniquely reconstructed given the other. Elhaik et al. made 4 major claims. 1) In the previous mapping system with the regular tetrahedron, calculation of the radius of the inscribed sphere is "a mathematical error". 2) S follows an exponential distribution and is narrowly distributed with a range of (0.25 - 0.33). 3) Based on the Chargaff's second parity rule (PR2), "S is equivalent to H [Shannon entropy]" and they are derivable from each other. 4) Z-curve "suffers from over dimensionality", because based on the analysis of 235 bacterial genomes, x and y components contributed only less than 1% of the variance and therefore "would be of little use". RESULTS: 1) Elhaik et al. mistakenly neglected the parameter [Formula: see text] when calculating the radius of the inscribed sphere. 2) The exponential distribution of S is a restatement of our previous conclusion, and the range of (0.25 - 0.33) only paraphrases the previously suggested S range (0.25 -1/3). 3) Elhaik et al. incorrectly disregard deviations from PR2 by treating the deviations as 0 altogether, reduce S and H, both having 4 variables, a, c, g and t, into functions of one single variable, a only, and apply this treatment to all DNA sequences as the basis of their "demonstration", which is therefore invalid. 4) Elhaik et al. confuse numeral smallness with biological insignificance, and disregard the distributions of purine/pyrimidine and amino/keto bases (x and y components), the variations of which, although can be less than that of GC content, contain rich information that is important and useful, such as in locating replication origins of bacterial and archaeal genomes, and in studies of gene recognition in various species. CONCLUSION: Elhaik et al. confuse S (a single number) with Z-curve (a series of 3D coordinates), which are distinct. To use S as a case study of Z-curve, by itself, is invalid. S and H are neither equivalent nor derivable from each other. The criticisms of Elhaik, Graur and Josic are wrong. REVIEWERS: This article was reviewed by Erik van Nimwegen.
ebbzx8yr
A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein
SARS-CoV-2 is a zoonotic virus that has caused a pandemic of severe respiratory disease—COVID-19— within several months of its initial identification. Comparable to the first SARS-CoV, this novel coronavirus’s surface Spike (S) glycoprotein mediates cell entry via the human ACE-2 receptor, and, thus, is the principal target for the development of vaccines and immunotherapeutics. Molecular information on the SARS-CoV-2 S glycoprotein remains limited. Here we report the crystal structure of the SARS-CoV-2 S receptor-binding-domain (RBD) at a the highest resolution to date, of 1.95 Å. We identified a set of SARS-reactive monoclonal antibodies with cross-reactivity to SARS-CoV-2 RBD and other betacoronavirus S glycoproteins. One of these antibodies, CR3022, was previously shown to synergize with antibodies that target the ACE-2 binding site on the SARS-CoV RBD and reduce viral escape capacity. We determined the structure of CR3022, in complex with the SARS-CoV-2 RBD, and defined a broadly reactive epitope that is highly conserved across betacoronaviruses. This epitope is inaccessible in the “closed” prefusion S structure, but is accessible in “open” conformations. This first-ever resolution of a human antibody in complex with SARS-CoV-2 and the broad reactivity of this set of antibodies to a conserved betacoronavirus epitope will allow antigenic assessment of vaccine candidates, and provide a framework for accelerated vaccine, immunotherapeutic and diagnostic strategies against SARS-CoV-2 and related betacoronaviruses. HIGHLIGHTS High resolution structure of the SARS-CoV-2 Receptor-Binding-Domain (RBD). Recognition of the SARS-CoV-2 RBD by SARS-CoV antibodies. Structure of the SARS-COV-2 RBD in complex with antibody CR3022. Identification of a cryptic site of vulnerability on the SARS-CoV-2 Spike.
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Spatial Disparities in Coronavirus Incidence and Mortality in the United States: An Ecological Analysis as of May 2020
PURPOSE: This ecological analysis investigates the spatial patterns of the COVID‐19 epidemic in the United States in relation to socioeconomic variables that characterize US counties. METHODS: Data on confirmed cases and deaths from COVID‐19 for 2,814 US counties were obtained from Johns Hopkins University. We used Geographic Information Systems (GIS) to map the spatial aspects of this pandemic and investigate the disparities between metropolitan and nonmetropolitan communities. Multiple regression models were used to explore the contextual risk factors of infections and death across US counties. We included population density, percent of population aged 65+, percent population in poverty, percent minority population, and percent of the uninsured as independent variables. A state‐level measure of the percent of the population that has been tested for COVID‐19 was used to control for the impact of testing. FINDINGS: The impact of COVID‐19 in the United States has been extremely uneven. Although densely populated large cities and their surrounding metropolitan areas are hotspots of the pandemic, it is counterintuitive that incidence and mortality rates in some small cities and nonmetropolitan counties approximate those in epicenters such as New York City. Regression analyses support the hypotheses of positive correlations between COVID‐19 incidence and mortality rates and socioeconomic factors including population density, proportions of elderly residents, poverty, and percent population tested. CONCLUSIONS: Knowledge about the spatial aspects of the COVID‐19 epidemic and its socioeconomic correlates can inform first responders and government efforts. Directives for social distancing and to “shelter‐in‐place” should continue to stem the spread of COVID‐19.
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Why coronavirus death rate is so hard to pin down
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Protein co-expression network analysis (ProCoNA)
BACKGROUND: Biological networks are important for elucidating disease etiology due to their ability to model complex high dimensional data and biological systems. Proteomics provides a critical data source for such models, but currently lacks robust de novo methods for network construction, which could bring important insights in systems biology. RESULTS: We have evaluated the construction of network models using methods derived from weighted gene co-expression network analysis (WGCNA). We show that approximately scale-free peptide networks, composed of statistically significant modules, are feasible and biologically meaningful using two mouse lung experiments and one human plasma experiment. Within each network, peptides derived from the same protein are shown to have a statistically higher topological overlap and concordance in abundance, which is potentially important for inferring protein abundance. The module representatives, called eigenpeptides, correlate significantly with biological phenotypes. Furthermore, within modules, we find significant enrichment for biological function and known interactions (gene ontology and protein-protein interactions). CONCLUSIONS: Biological networks are important tools in the analysis of complex systems. In this paper we evaluate the application of weighted co-expression network analysis to quantitative proteomics data. Protein co-expression networks allow novel approaches for biological interpretation, quality control, inference of protein abundance, a framework for potentially resolving degenerate peptide-protein mappings, and a biomarker signature discovery.
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Replication of an enteric bovine coronavirus in intestinal organ cultures
A coronavirus isolated in tracheal organ cultures from the faeces of a calf with diarrhoea readily multiplied on passage in intestinal organ cultures. Evidence for multiplication was obtained by the production of viral haemagglutinin in organ culture fluids and the presence of immunofluorescence and viral particles in the columnar epithelial cells of the villi. Thus virus multiplication was studiedin vitro in the cell type in which it multiplies naturally.
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Oklahoma to provide iPads for telehealth during pandemic
The Oklahoma Department of Mental Health and Substance Abuse is taking action to help those feeling depressed while home during the coronavirus pandemic, News 9 reported. Starting April 10, every city‐county health department in the state will be equipped with an iPad. Someone walk‐ing in needing help can use the iPad to speak with a mental health professional. The person can take the iPad home with them to continue conversations with the provider. “There's a button on it. They hit the button and it links up to community mental health providers in their area. Someone is able to talk with them and work through it,” said Carrie Slatton‐Hodges, the interim commissioner for the department. Eighty‐one sites across the state will have the iPads. Because of the state's large presence of telehealth technology, Slatton‐Hodges said the department has been able to continue performing 90% of services.
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Short term outcome and risk factors for mortality in adults with critical severe acute respiratory syndrome (SARS)
The independent risk factors to predict mortality of critical severe acute respiratory syndrome (SARS) were investigated. One hundred and two patients diagnosed with critical SARS were admitted to hospitals of Shanxi Province, from March 7, 2003 to June 4, 2003. The patients were prospectively studied after admission to access their short term outcomes and the risk factors associated with adverse outcomes, defined as death. All the demographic and clinical characteristics were studied and univariate and multivariate Logistic regression were employed to access the risk factors. The results showed that of the 102 cases, 23 patients died, with a crude mortality rate of 22.5%. Multivariate Logistic regression revealed that age above 50 [odds ratio (OR) 1. 10, 95% confidence internal (CI) 1.03 to 1.16,P=0.004], lymphopenia at early stage (OR 14.62, 95% CI 1.78 to 11.97,P=0.01) were independently associated with mortality. On the other side, psychotherapy (OR 0.01, 95% CI 0.00 to 0.06,P<0.001) was independently associated with aliveness. It was concluded that critical SARS is a new disease entity that carries significant mortality and morbidity. Specific clinical and laboratory parameters predicting unfavorable and favorable outcomes have been identified.
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The role of a cytokine storm in severe COVID-19 disease in pregnancy
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The sequence of cDNA of bovine coronavirus 32K nonstructural gene.
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Effects of the Toll-like receptor 7 (TLR7) agonist, AZD8848, on allergen-induced responses in patients with mild asthma: a double-blind, randomised, parallel-group study
BACKGROUND: Although allergic asthma is a complex area with many interacting factors involved, the ‘hygiene hypothesis’ proposes that a lack of exposure to infection during childhood may polarise the immune system towards allergen-reactive Th2-type responses in genetically susceptible individuals. Toll-like receptors (TLRs) play a key role within the innate immune system and TLR7 agonists have previously been shown to up-regulate Th1 responses and down-regulate Th2 responses to allergens in murine models of allergic or chronic asthma. This study aimed to examine the efficacy and safety of the novel TRL7 agonist AZD8848, which has been developed as an antedrug. METHODS: In this double-blind, randomised, parallel-group study, AZD8848 60 μg or placebo was administered intranasally once-weekly for 8 weeks in patients with mild-to-moderate allergic asthma (NCT00999466). Efficacy assessments were performed at 1 and 4 weeks after the last dose. The primary outcome was the late asthmatic response (LAR) fall in forced expiratory volume in 1 s (FEV(1)) after allergen challenge at 1-week post-treatment. RESULTS: AZD8848 significantly reduced average LAR fall in FEV(1) by 27% vs. placebo at 1 week after treatment (p = 0.035). This effect was sustained at 4 weeks post-treatment; however, it did not reach clinical significance. AZD8848 reduced post-allergen challenge methacholine-induced airway hyper-responsiveness (AHR) vs. placebo at 1 week post-dosing (treatment ratio: 2.20, p = 0.024), with no effect at 4 weeks. There was no significant difference between the two groups in plasma cytokine, sputum Th2 cytokine or eosinophil responses post-allergen challenge at 1 week after treatment. The incidence of adverse events was similar in the two groups. AZD8848 was generally well tolerated. CONCLUSIONS AND CLINICAL RELEVANCE: In patients with allergic asthma, TLR7 agonists could potentially reduce allergen responsiveness by stimulating Type 1 interferon responses to down-regulate the dominant Th2 responses. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT00999466.
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Inhibition of HIV-1 by multiple siRNAs expressed from a single microRNA polycistron
RNA interference (RNAi) is a powerful approach to inhibit human immunodeficiency virus type 1 (HIV-1) replication. However, HIV-1 can escape from RNAi-mediated antiviral therapy by selection of mutations in the targeted sequence. To prevent viral escape, multiple small interfering RNAs (siRNAs) against conserved viral sequences should be combined. Ideally, these RNA inhibitors should be expressed simultaneously from a single transgene transcript. In this study, we tested a multiplex microRNA (miRNA) expression strategy by inserting multiple effective anti-HIV siRNA sequences in the miRNA polycistron mir-17-92. Individual anti-HIV miRNAs that resemble the natural miRNA structures were optimized by varying the siRNA position in the hairpin stem to obtain maximal effectiveness against luciferase reporters and HIV-1. We show that an antiviral miRNA construct can have a greater intrinsic inhibitory activity than a conventional short hairpin (shRNA) construct. When combined in a polycistron setting, the silencing activity of an individual miRNA is strongly boosted. We demonstrate that HIV-1 replication can be efficiently inhibited by simultaneous expression of four antiviral siRNAs from the polycistronic miRNA transcript. These combined results indicate that a multiplex miRNA strategy may be a promising therapeutic approach to attack escape-prone viral pathogens.
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Solving the COVID-19 Crisis in Post-Acute and Long-Term Care
Abstract Our nation’s nursing home industry has been in need of overhaul for decades – a situation made all the more evident by COVID-19. AMDA – The Society of Post-Acute and Long-Term Care Medicine is dedicated to quality in post-acute and long-term care (PALTC) process and outcomes. This special article presents five keys to solving the COVID-19 crisis in PALTC, related to policy, collaboration, individualization, leadership, and reorganization. Taking action during this crisis may prevent sinking back into the complacency and habits of our pre-COVID-19 lives.
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Twelve years' detection of respiratory viruses by immunofluorescence in hospitalised children: impact of the introduction of a new respiratory picornavirus assay
BACKGROUND: Direct immunofluorescence assays (DFA) are a rapid and inexpensive method for the detection of respiratory viruses and may therefore be used for surveillance. Few epidemiological studies have been published based solely on DFA and none included respiratory picornaviruses and human metapneumovirus (hMPV). We wished to evaluate the use of DFA for epidemiological studies with a long-term observation of respiratory viruses that includes both respiratory picornaviruses and hMPV. METHODS: Since 1998 all children hospitalized with respiratory illness at the University Hospital Bern have been screened with DFA for common respiratory viruses including adenovirus, respiratory syncytial virus (RSV), influenza A and B, and parainfluenza virus 1-3. In 2006 assays for respiratory picornaviruses and hMPV were added. Here we describe the epidemiological pattern for these respiratory viruses detected by DFA in 10'629 nasopharyngeal aspirates collected from 8'285 patients during a 12-year period (1998-2010). RESULTS: Addition of assays for respiratory picornaviruses and hMPV raised the proportion of positive DFA results from 35% to 58% (p < 0.0001). Respiratory picornaviruses were the most common viruses detected among patients ≥1 year old. The seasonal patterns and age distribution for the studied viruses agreed well with those reported in the literature. In 2010, an hMPV epidemic of unexpected size was observed. CONCLUSIONS: DFA is a valid, rapid, flexible and inexpensive method. The addition of assays for respiratory picornaviruses and hMPV broadens its range of viral detection. DFA is, even in the "PCR era", a particularly adapted method for the long term surveillance of respiratory viruses in a pediatric population.
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Telehealth Policies Impacting Federally Qualified Health Centers in Face of COVID‐19
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Stroke care in Europe during the COVID‐19 pandemic
In view of finite health care resources and the ethical principle of distributive justice, healthcare systems across Europe have been adapted to provide care for patients with coronavirus disease 2019 (COVID‐19) while not neglecting other serious medical emergencies. Policies to contain disease spreading and to preserve usual health care systems as much as possible differ considerably between countries.
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Barrier Shields: Not Just for Intubations in Today’s COVID-19 World?
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Be Prepared
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Computational Comparison and Visualization of Viruses in the Perspective of Clinical Information
This paper addresses the visualization of complex information using multidimensional scaling (MDS). MDS is a technique adopted for processing data with multiple features scattered in high-dimensional spaces. For illustrating the proposed techniques, the case of viral diseases is considered. The study evaluates the characteristics of 21 viruses in the perspective of clinical information. Several new schemes are proposed for improving the visualization of the MDS charts. The results follow standard clinical practice, proving that the method represents a valuable tool to study a large number of viruses.
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TMPRSS2 and MSPL Facilitate Trypsin-Independent Porcine Epidemic Diarrhea Virus Replication in Vero Cells
Type II transmembrane serine proteases (TTSPs) facilitate the spread and replication of viruses such as influenza and human coronaviruses, although it remains unclear whether TTSPs play a role in the progression of animal coronavirus infections, such as that by porcine epidemic diarrhea virus (PEDV). In this study, TTSPs including TMPRSS2, HAT, DESC1, and MSPL were tested for their ability to facilitate PEDV replication in Vero cells. Our results showed that TMPRSS2 and MSPL played significant roles in the stages of cell–cell fusion and virus–cell fusion, whereas HAT and DESC1 exhibited weaker effects. This activation may be involved in the interaction between TTSPs and the PEDV S protein, as the S protein extensively co-localized with TMPRSS2 and MSPL and could be cleaved by co-expression with TMPRSS2 or MSPL. Moreover, the use of Vero cells expressing TMPRSS2 and MSPL facilitated PEDV replication in the absence of exogenous trypsin. In sum, we identified two host proteases, TMPRSS2 and MSPL, which may provide insights and a novel method for enhancing viral titers, expanding virus production, and improving the adaptability of PEDV isolates in vitro.
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Impact of vitamins A, B, C, D, and E supplementation on improvement and mortality rate in ICU patients with coronavirus-19: a structured summary of a study protocol for a randomized controlled trial
OBJECTIVES: This study will evaluate the main hypothesis that supplementation with vitamins A, B, C, D, and E significantly improves the severity and mortality rate in ICU patients with COVID-19. TRIAL DESIGN: This study is a randomized, single-blinded, two-arm (1:1 ratio) parallel group clinical trial. PARTICIPANTS: We are conducting this study in patients with COVID-19 admitted to intensive care units at the Imam Khomeini Hospital Complex in Tehran, Iran. The inclusion criteria are as follows: (1) aged between 20 and 60 years, (2) both male and female patients with COVID-19, (3) clinical or definitive diagnosis (using polymerase chain reaction (PCR) test), (4) patients have not participated in other clinical trials, and (5) no renal or hepatic abnormalities. The exclusion criteria are as follows: (1) patients with specific and rare viral diseases such as HIV and (2) patients who have been undergoing chemotherapy for the past month. INTERVENTION AND COMPARATOR: Duration of intervention: 7 days from randomization Vitamin A 25,000 IU daily. Vitamin D 600,000 IU once during study. Vitamin E 300 IU twice daily. Vitamin C is taken four times per day. B vitamins are taken as a daily Soluvit [which included thiamine nitrate 3.1 mg, sodium riboflavin phosphate 4.9 mg (corresponding to vitamin B(2) 3.6 mg), nicotinamide 40 mg, pyridoxine hydrochloride 4.9 mg (corresponding to vitamin B(6) 4.0 mg), sodium pantothenate 16.5 mg (corresponding to pantothenic acid 15 mg), sodium ascorbate 113 mg (corresponding to vitamin C 100 mg), biotin 60 μg, folic acid 400 μg, and cyanocobalamin 5 μg]. The control group will not receive any supplements or placebo. All supplements are made in Iran except for Soluvit (from Fresenius Kabi, New Zealand). MAIN OUTCOMES: 1. Weight, height, and BMI. 2. Severity of pulmonary involvement according to CT scan. 3. Respiratory support (invasive or non-invasive). 4. Percentage of oxygen saturation (SpO2 level). 5. Serum levels of WBC, CRP, ESR, IL6, IFN-G, and TNF-α. 6. The patient’s body temperature. 7. The presence or absence of involvement of organs other than the lungs (e.g., heart, liver, kidneys). 8. Duration of hospitalization. 9. Mortality rate. RANDOMIZATION: At baseline, eligible patients were randomly assigned to a 1:1 ratio to one of two groups: intervention and control. Block randomization is used based on the gender of patients. BLINDING (MASKING): Patients are unaware of being placed in the intervention or control groups after signing consent. All treatment staff will be aware of which group each of the patients is in due to the specific conditions of the ICU and the absence of placebo for the control group. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The researchers plan to include 60 patients in total, with 30 patients in each group. TRIAL STATUS: This is the first version of the protocol which started on April 2, 2020. Recruitment began April 2, 2020, and is expected to be complete by July 4, 2020. TRIAL REGISTRATION: The Iranian Registry of Clinical Trials IRCT20200319046819N1. Registered on April 4, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol (Fig. 1, Table 1).
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Proteasome inhibition in cancer is associated with enhanced tumor targeting by the adeno‐associated virus/phage
Bacteriophage (phage), which are viruses that infect bacteria only, have shown promise as vehicles for targeted cancer gene therapy, albeit with poor efficiency. Recently, we generated an improved version of phage vectors by incorporating cis genetic elements of adeno‐associated virus (AAV). This novel AAV/phage hybrid (AAVP) efficiently delivered systemically administered therapeutic genes to various tumor targets by displaying an integrin tumor‐targeting ligand on the phage capsid. However, inherent limitations in bacteriophage mean that these AAVP vectors still need to be improved. One of the limitations of AAVP in mammalian cells may be its susceptibility to proteasomal degradation. The proteasome is upregulated in cancer and it is known that it constitutes a barrier to gene delivery by certain eukaryotic viruses. We report here that inhibition of proteasome improved targeted reporter gene delivery by AAVP in cancer cells in vitro and in tumors in vivo after intravenous vector administration to tumor‐bearing mice. We also show enhanced targeted tumor cell killing by AAVP upon proteasome inhibition. The AAVP particles persisted significantly in cancer cells in vitro and in tumors in vivo after systemic administration, and accumulated polyubiquitinated coat proteins. Our results suggest that the proteasome is indeed a barrier to tumor targeting by AAVP and indicate that a combination of proteasome‐inhibiting drugs and AAVP should be considered for clinical anticancer therapy.
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Prevalence and molecular characterization of infectious bronchitis virus isolated from chicken in Bangladesh
AIM: The present study was aimed to determine the prevalence of infectious bronchitis virus (IBV) as well as virus isolation, identification, and molecular characterization of various strains circulating in Bangladesh. MATERIALS AND METHODS: A total of 371 swabs and organ samples were collected from four types of chicken including layer, Sonali (local), broiler, and broiler breeder under eight districts (Rangpur, Bogura, Tangail, Dhaka, Gazipur, Mymensingh, Jamalpur, and Cumilla) during 2014-2016 in Bangladesh. RESULTS: Out of 371 samples, 65 samples were positive in reverse transcriptase polymerase chain reaction (RT-PCR) for molecular identification of IBV. The overall prevalence was 17.52% recorded and among the selected types of chicken, the highest prevalence of IBV was found in layer that was 42.22% followed by 17.24% in Sonali, 14.93% in broiler breeder, and lowest prevalence was 11.94% in broiler chicken, respectively. Moreover, the prevalence of IBV was recorded highest in aged chicken at 41-60 weeks, which was 54.55% in layer, 27.27% in Sonali, and, afterward, 14.68% was found in broiler breeder, respectively. Frequency of IBV more frequently in winter (22.67%) followed by rainy (15.87%) and summer season (11.58%). The highest prevalence of IBV was found Tangail district (41.67%) followed by Mymensingh (24.42%), Gazipur (19.32%), Dhaka (15.38%), Jamalpur (16.67%), Bogura (13.68%), Cumilla (5.88%), and Rangpur (9.26%), respectively. Samples that were found high positive in IBV RT-PCR (Ct value below 30) were subjected to inoculation into chicken egg embryo to observe characteristic changes in chicken embryo. Swabs and organ samples were processed and passaged in 9-day-old embryonated chicken eggs through allantoic cavity route. IBV virus suspected samples inoculated into chicken egg embryos after 3-5 passages showed dwarfing and curling of the embryos which are characteristic lesions of IBV. Allantoic fluid was collected from all inoculated eggs and performed partial sequencing of S1 gene for three isolates. After sequencing, the phylogenetic tree was constructed from the nucleotide sequences of IBV isolates. Two of the isolates are 4/91 IBV and another one matched with QX-like IBV. CONCLUSION: The results revealed that the three isolates from different places in Bangladesh were identified for the 1(st) time as which will help for IBV control strategy.
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Diabetes and severity of COVID-19: what is the link?
In Diabetes Mellitus the loss of capacity to regulate immunity, the reduction of pulmonary functions and the pro-thrombotic state determine the severity of COVID-19.
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Kawasaki syndrome and concurrent Coxsackie virus B3 infection
We describe two previously healthy children who were hospitalized in the same period in different departments of our University with clinical signs of Kawasaki syndrome, which were treated with intravenous immunoglobulins and acetylsalicylic acid: in both cases, Coxsackie virus infection was concurrently demonstrated by enzyme-linked immunosorbent assay, and complement fixation test identified antibodies to serotype B3. In the acute phase, both patients presented hyperechogenic coronary arteries, but no cardiologic sequels in the mid term. The etiological relationship between Kawasaki syndrome and Coxsackie viruses is only hypothetical; however, the eventual identification of ad hoc environmental triggers is advisable in front of children with Kawasaki syndrome, with the aim of optimizing epidemiological surveillance and understanding the intimate biological events of this condition.
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Of plagues, planes and politics: Controlling the global spread of infectious diseases by air
Abstract In recent years, the implications of globalisation for the spread of infectious diseases has begun to emerge as an area of concern to political geographers. Unsurprisingly, much of the contemporary literature focuses on the multifarious threats posed by human and, increasingly, non-human mobility. Prompted by current geopolitical concerns surrounding the public health implications of regular international air travel, this paper extends such research by exploring the ways in which the technology of the aeroplane stimulated the production of new international sanitary initiatives aimed at safeguarding global public health in an era of mass aeromobility. By tracing the development of sanitary regulations for aerial navigation, from their origins in the 1920s through the twentieth century in particular, we document the emergence of a series of public health interventions that were designed to limit the public health threat associated with increased international air travel and the concomitant rise in the mobility of infectious diseases. From inoculation certificates to quarantine and the routine ‘disinsection’ of passenger aircraft with powerful insecticides, modern air travel is replete with a complex set of procedures designed to lessen the risks associated with flying between different climatic and ecological zones. Our detailed examination of the historical context in which these procedures were devised and implemented leads us to consider the importance of time and space, power and efficacy, to the development of a more nuanced understanding of the shifting public health response to an increasingly fluid, mobile, and inter-connected society.
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SARS-CoV2 coronavirus: So far polite with children. Debatable immunological and non-immunological evidence
Abstract The reasons for the relative resistance of children to certain infections such as that caused by coronavirus SARS- CoV2 are not yet fully clear. Deciphering these differences can provide important information about the pathogenesis of the disease. Regarding the SARS-CoV2 virus, children are at the same risk of infection as the general population of all ages, with the most serious cases being found in infants. However, it has been reported that the disease is much less frequent than in adults and that most cases are benign or moderate (even with high viral loads), provided there are no other risk factors or underlying diseases. It is not clear why they have lower morbidity and virtually no mortality. A series of findings, relationships and behavioral patterns between the infectious agent and the child host may account for the lower incidence and a greatly attenuated clinical presentation of the disease in children.
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Dendritic Cells
Abstract T cells are an essential element that regulates the balance in immunity, by killing infected cells, helping antibody formation and suppressing autoimmune responses. However, T cells are incapable of recognizing native antigens. Instead, they recognize processed peptides presented by MHC molecules. Dendritic cells (DCs) are professional antigen presenting cells that inform the fight against invasive pathogens while enforcing tolerance to self and harmless environmental antigens. They capture pathogens and receive signals from pathogens that influence the outcome of immune responses. On the basis of these signals, DCs orchestrate antigen specific T cell differentiation. Alternatively they can silence self-reactive T cells by inducing deletion, anergy or regulation (Treg). This article will discuss the discovery, function and development of DCs and the mechanisms by which they link innate immunity to adaptive immunity.
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Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review
BACKGROUND: The coronavirus disease (COVID-19) has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. As of 31 January 2020, this epidemic had spread to 19 countries with 11 791 confirmed cases, including 213 deaths. The World Health Organization has declared it a Public Health Emergency of International Concern. METHODS: A scoping review was conducted following the methodological framework suggested by Arksey and O’Malley. In this scoping review, 65 research articles published before 31 January 2020 were analyzed and discussed to better understand the epidemiology, causes, clinical diagnosis, prevention and control of this virus. The research domains, dates of publication, journal language, authors’ affiliations, and methodological characteristics were included in the analysis. All the findings and statements in this review regarding the outbreak are based on published information as listed in the references. RESULTS: Most of the publications were written using the English language (89.2%). The largest proportion of published articles were related to causes (38.5%) and a majority (67.7%) were published by Chinese scholars. Research articles initially focused on causes, but over time there was an increase of the articles related to prevention and control. Studies thus far have shown that the virus’ origination is in connection to a seafood market in Wuhan, but specific animal associations have not been confirmed. Reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines have been discussed as ways to reduce transmission. To date, no specific antiviral treatment has proven effective; hence, infected people primarily rely on symptomatic treatment and supportive care. CONCLUSIONS: There has been a rapid surge in research in response to the outbreak of COVID-19. During this early period, published research primarily explored the epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus. Although these studies are relevant to control the current public emergency, more high-quality research is needed to provide valid and reliable ways to manage this kind of public health emergency in both the short- and long-term.
fhmhpobi
Virus infection-induced host mRNA degradation and potential application of live cell imaging
Abstract Viruses exist wherever there is life. They can cause allergy, immune response, inflammation, and even fatal diseases directly or indirectly. Accumulating evidence shows that host RNA undergoes rapid degradation during virus infection. Herein, we focus on several possible mechanisms of infection-induced host RNA turnover, which seems to be a common strategy for both prokaryotic and eukaryotic viruses during the very early stage of infection and a potential application of live cell imaging on its visualization.
7etq1vec
Non-invasive ventilation in acute respiratory failure
Summary Non-invasive mechanical ventilation has been increasingly used to avoid or serve as an alternative to intubation. Compared with medical therapy, and in some instances with invasive mechanical ventilation, it improves survival and reduces complications in selected patients with acute respiratory failure. The main indications are exacerbation of chronic obstructive pulmonary disease, cardiogenic pulmonary oedema, pulmonary infiltrates in immunocompromised patients, and weaning of previously intubated stable patients with chronic obstructive pulmonary disease. Furthermore, this technique can be used in postoperative patients or those with neurological diseases, to palliate symptoms in terminally ill patients, or to help with bronchoscopy; however further studies are needed in these situations before it can be regarded as first-line treatment. Non-invasive ventilation implemented as an alternative to intubation should be provided in an intensive care or high-dependency unit. When used to prevent intubation in otherwise stable patients it can be safely administered in an adequately staffed and monitored ward.
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Heterotypic Infection and Spread of Rhinovirus A, B, and C among Childcare Attendees
BACKGROUND: Despite the frequency of human rhinovirus (HRV), data describing the molecular epidemiology of HRV in the community are limited. Childcare centers are optimal settings to characterize heterotypic HRV cocirculation. METHODS: HRV specimens were prospectively obtained from a cohort of childcare attendees at enrollment and weekly during respiratory illness. The 5′ noncoding region sequences were used to determine HRV species (A, B, C) and genotypes. RESULTS: Among 225 children followed, sequence data were available for 92 HRV infections: HRV-A (n = 80; 59%) was most common, followed by HRV-C (n = 52, 39%), and HRV-B (n = 3, 2%). Forty-one genotypes were identified and cocirculation was common. Frequent spread between classrooms occurred with 2 HRV-A genotypes. Repeated detections within single illnesses were a combination of persistent (n = 7) and distinct (n = 7) genotypes. Prevalence of HRV among asymptomatic children was 41%. HRV-C was clinically similar to HRV-A and HRV-B. CONCLUSIONS: HRV epidemiology in childcare consists of heterotypic cocirculation of genotypes with periodic spread within and among classrooms. Based on our finding of multiple genotypes evident during the course of single illnesses, the use of sequence-based HRV type determination is critical in longitudinal studies of HRV epidemiology and transmission.
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Clinical Course and Outcomes of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. METHODS: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. RESULTS: The median age was 40 years (range, 20–73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5–7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). CONCLUSION: The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.
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Hydatidiform mole in the era of COVID‐19 pandemic. Is there an association?
Coronavirus disease 2019 (COVID‐19) is considered a worldwide pandemic. COVID‐19 patients had profound immune dysregulation so they could be susceptible for adverse pregnancy outcomes as hydatidiform mole. In this article, we tried to explain the link between hydatidiform mole and COVID‐19.
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Available Evidence of Association between Zika Virus and Microcephaly
OBJECTIVE: To clarify the possible association between the Zika virus (ZIKV) and microcephaly and understand where we are in terms of research and the debate on the causation between mild maternal clinical features and severe fetal microcephaly. DATA SOURCES: We did a comprehensive literature review with the keywords “zika” and/or “microcephaly” from inception to May 27, 2016, with PubMed. STUDY SELECTION: Studies were included and analyzed if they met all of the following criteria: “probable or confirmed infant microcephaly” and “probable or confirmed ZIKV infection among mothers or infants”. RESULTS: We emphasize the diagnosis of ZIKV infection, including maternal clinical manifestations, maternal and fetal laboratory confirmation, and possible autopsy if need. Other confounders that may lead to microcephaly should be excluded from the study. We presented the results from clinical manifestations of ZIKV infection, testing methods evolving but the mechanism of microcephaly uncertain, flexible definition challenging the diagnosis of microcephaly, and limited causal reference on pregnant women. We made analog comparison of severe acute respiratory syndrome and chikungunya virus in terms of DNA mutation and global movement to provide further research recommendation. The chance of catch-up growth may decrease the number of pervious “diagnosed” microcephaly. CONCLUSIONS: There are some evidence available through mice models and direct isolation of ZIKV in affected pregnancies on kindly causal relationship but not convincible enough. We analyzed and presented the weakness or limitation of published reports with the desire to shed light to further study directions.
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Practical Guidelines for Collection, Manipulation and Inactivation of SARS‐CoV‐2 and COVID‐19 Clinical Specimens
SARS‐CoV‐2 is a novel coronavirus that causes the acute respiratory disease—Coronavirus disease 2019 (COVID‐19)—which has led to a global health crisis. Currently, no prophylactics or therapies exist to control virus spread or mitigate the disease. Thus, the risk of infection for physicians and scientists is high, requiring work to be conducted in Biosafety Level‐3 (BSL‐3) facilities if virus will be isolated or propagated. However, inactivation of the virus can enable safe handling at a reduced biosafety level, making samples accessible to a diverse array of institutions and investigators. Institutions of all types have an immediate need for guidelines that outline safe collection, handling, and inactivation of samples suspected to contain active virus. Here we provide a practical guide for physicians and researchers wishing to work with materials from patients who are COVID‐19 positive or suspected positive. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Practical guidelines for the safe collection and handling of specimens collected from COVID‐19 and suspected COVID‐19 patients Basic Protocol 2: Inactivating SARS‐CoV‐2
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Modern approaches to understanding stress and disease susceptibility: A review with special emphasis on respiratory disease
Studies in animals and humans link both physical and psychological stress with an increased incidence and severity of respiratory infections. For this manuscript we define stress as the physiological responses an individual undergoes while adjusting to a continually changing environment. It is known that stressors of various types (psychological/physical) can alter the physiological levels of certain hormones, chemokines and cytokines. These alterations send information to the central nervous system to take necessary action which then sends messages to appropriate organs/tissues/cells to respond. These messages can either activate or suppress the immune system as needed and failure to compensate for this by the body can lead to serious health-related problems. Little is known how stress affects disease susceptibility, yet understanding this mechanism is important for developing effective treatments, and for improving health and food quality. The current review focuses on (a) the effects of psychological stressors in humans and animals, (b) various methodologies employed to understand stress responses and their outcomes, and (c) the current status of the attempts to correlate stress and disease with respiratory disease as model system. The methodologies included in this review span traditional epidemiological, behavioral and immunological studies to current high throughput genomic, proteomic, metabolomic/metabonomic approaches. With the advent of various newer omics and bioinformatics methodologies we postulate that it will become feasible to understand the mechanisms through which stress can influence disease onset. Although the literature in this area is limited because of the infancy of this research area, the objective of this review is to illustrate the power of new approaches to address complex biological questions. These new approaches will also aid in our understanding how these processes are related to the dynamics and kinetics of changes in expression of multiple genes at various levels.
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Porcine epidemic diarrhea (PED) infection, diagnosis and vaccination: A mini review
Porcine epidemic diarrhea virus (PEDV) is a main etiology causing severe enteric disease in piglets with clinical signs of anorexia, vomiting, diarrhea and dehydration resulting in loss of condition and death within a few days. Historically, PED is one of major causes of loss in swine and remains prevalent in some parts of the world. Even with increase in the available tests for PED diagnosis, which include histological diagnosis; virological diagnosis and serological diagnosis, there is no vaccine or specific treatment for this disease yet. In this mini review, the overview and current situation of PED is described with updated techniques, in an effort to comprehensively discuss and understand the disease characteristics.
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The rationale for the use of colchicine in COVID-19: comments on the letter by Cumhur Cure M et al.
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Double trouble: methanol outbreak in the wake of the COVID-19 pandemic in Iran—a cross-sectional assessment
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Unhealthy Landscapes: Policy Recommendations on Land Use Change and Infectious Disease Emergence
Anthropogenic land use changes drive a range of infectious disease outbreaks and emergence events and modify the transmission of endemic infections. These drivers include agricultural encroachment, deforestation, road construction, dam building, irrigation, wetland modification, mining, the concentration or expansion of urban environments, coastal zone degradation, and other activities. These changes in turn cause a cascade of factors that exacerbate infectious disease emergence, such as forest fragmentation, disease introduction, pollution, poverty, and human migration. The Working Group on Land Use Change and Disease Emergence grew out of a special colloquium that convened international experts in infectious diseases, ecology, and environmental health to assess the current state of knowledge and to develop recommendations for addressing these environmental health challenges. The group established a systems model approach and priority lists of infectious diseases affected by ecologic degradation. Policy-relevant levels of the model include specific health risk factors, landscape or habitat change, and institutional (economic and behavioral) levels. The group recommended creating Centers of Excellence in Ecology and Health Research and Training, based at regional universities and/or research institutes with close links to the surrounding communities. The centers’ objectives would be 3-fold: a) to provide information to local communities about the links between environmental change and public health; b) to facilitate fully interdisciplinary research from a variety of natural, social, and health sciences and train professionals who can conduct interdisciplinary research; and c) to engage in science-based communication and assessment for policy making toward sustainable health and ecosystems.
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Stable long‐term cultures of self‐renewing B cells and their applications
Monoclonal antibodies are essential therapeutics and diagnostics in a large number of diseases. Moreover, they are essential tools in all sectors of life sciences. Although the great majority of monoclonal antibodies currently in use are of mouse origin, the use of human B cells to generate monoclonal antibodies is increasing as new techniques to tap the human B cell repertoire are rapidly emerging. Cloned lines of immortalized human B cells are ideal sources of monoclonal antibodies. In this review, we summarize our studies to the regulation of the replicative life span, differentiation, and maturation of B cells that led to the development of a platform that uses immortalization of human B cells by in vitro genetic modification for antibody development. We describe a number of human antibodies that were isolated using this platform and the application of the technique in other species. We also discuss the use of immortalized B cells as antigen‐presenting cells for the discovery of tumor neoantigens.
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Full genome analysis of a novel type II feline coronavirus NTU156
Infections by type II feline coronaviruses (FCoVs) have been shown to be significantly correlated with fatal feline infectious peritonitis (FIP). Despite nearly six decades having passed since its first emergence, different studies have shown that type II FCoV represents only a small portion of the total FCoV seropositivity in cats; hence, there is very limited knowledge of the evolution of type II FCoV. To elucidate the correlation between viral emergence and FIP, a local isolate (NTU156) that was derived from a FIP cat was analyzed along with other worldwide strains. Containing an in-frame deletion of 442 nucleotides in open reading frame 3c, the complete genome size of NTU156 (28,897 nucleotides) appears to be the smallest among the known type II feline coronaviruses. Bootscan analysis revealed that NTU156 evolved from two crossover events between type I FCoV and canine coronavirus, with recombination sites located in the RNA-dependent RNA polymerase and M genes. With an exchange of nearly one-third of the genome with other members of alphacoronaviruses, the new emerging virus could gain new antigenicity, posing a threat to cats that either have been infected with a type I virus before or never have been infected with FCoV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-012-0864-0) contains supplementary material, which is available to authorized users.
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MAVS-MKK7-JNK2 Defines a Novel Apoptotic Signaling Pathway during Viral Infection
Viral infection induces innate immunity and apoptosis. Apoptosis is an effective means to sacrifice virus-infected host cells and therefore restrict the spread of pathogens. However, the underlying mechanisms of this process are still poorly understood. Here, we show that the mitochondrial antiviral signaling protein (MAVS/VISA/Cardif/IPS-1) is critical for SeV (Sendai virus)-induced apoptosis. MAVS specifically activates c-Jun N-terminal kinase 2 (JNK2) but not other MAP kinases. Jnk2−/− cells, but not Jnk1−/− cells, are unable to initiate virus-induced apoptosis and SeV further fails to trigger apoptosis in MAPK kinase 7 (MKK7) knockout (Mkk7−/−) cells. Mechanistically, MAVS recruits MKK7 onto mitochondria via its 3D domain, which subsequently phosphorylates JNK2 and thus activates the apoptosis pathway. Consistently, Jnk2−/− mice, but not Jnk1−/− mice, display marked inflammatory injury in lung and liver after viral challenge. Collectively, we have identified a novel signaling pathway, involving MAVS-MKK7-JNK2, which mediates virus-induced apoptosis and highlights the indispensable role of mitochondrial outer membrane in host defenses.
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Complete genomic sequence of the coronavirus transmissible gastroenteritis virus SHXB isolated in China
A strain of transmissible gastroenteritis virus (TGEV), SHXB, was isolated in Shanghai, China. The complete genome of strain SHXB was sequenced, and its sequence was compared those of other TGEV strains in the GenBank database. The comparison showed that there were no insertions or deletions in the 5′ and 3′- non-translated regions, in the nonstructural genes ORF1, ORF3, and ORF7, or in the genes encoding the structural proteins envelope (E), membrane (M) and nucleoprotein (N). A phenomenon in common with other strains was that nucleotide (nt) 655 of the spike (S) gene was G, and a common change in nt 1753 of the S gene was a T-to-G mutation that caused a serine-to-alanine mutation at amino acid 585, which is in the region of the main major antigenic sites A and B of the TGEV S protein. A 6-nt deletion was also found at nt 1123-1128 in all Purdue strains except the strain Virulent Purdue. Phylogenetic analysis showed that TGEV SHXB was closely related to the Purdue strains and shared a common ancestor with the Miller strains as well as strain PRCV-ISU-1. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-014-2080-9) contains supplementary material, which is available to authorized users.
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Diagnostic strategies for SARS-CoV-2 infection and interpretation of microbiological results
BACKGROUND: To face the current COVID-19 pandemic, diagnostic tools are essential. It is recommended to use real-time RT-PCR for RNA viruses in order (i) to perform a rapid and accurate diagnostic, (ii) to guide patient care and management and (iii) to guide epidemiological strategies. Further studies are warranted to define the role of serological diagnosis and a possible correlation between serological response and prognosis. OBJECTIVES: To guide clinical microbiologists in the use of these diagnostic tests and clinicians in the interpretation of their results. SOURCES: A research of literature was performed through PubMed and Google Scholar using the keywords SARS-CoV-2, SARS-CoV-2 molecular diagnosis, SARS-CoV-2 immune response, SARS-CoV-2 serology/antibody testing, coronavirus diagnosis. CONTENT: The present review discusses performances, limitations and use of current and future diagnostic tests for SARS-CoV-2. IMPLICATIONS: Real-time RT-PCR remains the reference method for diagnosis of SARS-CoV-2 infection. On the other hand, notwithstanding its varying sensitivity according to the time of infection, serology represents a valid asset (i) to try to solve possible discrepancies between a highly suggestive clinical and radiological presentation and negative RT-PCR, (ii) to solve discrepancies between different PCR assays, and (iii) for epidemiological purposes.
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Considerations for Management of Acute Coronary Syndromes During the SARS-CoV-2 (COVID-19) Pandemic
Accumulating evidence suggests that influenza and influenza-like illnesses can act as a trigger for acute myocardial infarction (AMI). Despite these unprecedented times providers should not overlook ACS guidelines, but may choose to modify the recommended approach in situations with confirmed or suspected COVID-19 disease. In this document, we suggest recommendations as to how to triage patients diagnosed with acute coronary syndromes (ACS) and provide with algorithms of how to manage the patients and decide the appropriate treatment options in the era of COVID-19 pandemic. We also address the inpatient logistics and discharge to follow-up considerations for the function of already established ACS network during the pandemic.
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SYBR Green real-time reverse transcription-polymerase chain reaction assay for the generic detection of coronaviruses
Coronaviruses are etiologic agents of respiratory and enteric diseases in humans and in animals. In this study, a one-step real-time reverse transcription-polymerase chain reaction (RT-PCR) assay based on SYBR Green chemistry and degenerate primers was developed for the generic detection of coronaviruses. The primers, designed in the open reading frame 1b, enabled the detection of 32 animal coronaviruses including strains of canine coronavirus, feline coronavirus, transmissible gastroenteritis virus (TGEV), bovine coronavirus (BCoV), murine hepatitis virus (MHV) and infectious bronchitis virus (IBV). A specific amplification was also observed with the human coronaviruses (HCoV) HCoV-NL63, HCoV-OC43, HCoV-229E and severe acute respiratory syndrome coronavirus (SARS-CoV). The real-time RT-PCR detected down to 10 cRNA copies from TGEV, BCoV, SARS-CoV and IBV. In addition, the assay exhibited a high sensitivity and specificity on clinical samples from different animal species. The developed assay represents a potential tool for laboratory diagnostics and for detecting still uncharacterized coronaviruses.
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Abstract 44. Paramyxovi rus induced changes of β-adrenergic receptor response and its immunological modulation
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Lack of viral transmission to preterm newborn from a COVID‐19 positive breastfeeding mother at 11 days postpartum
In December 2019, novel coronavirus 2019 has appeared in China. On 11 February 2020, the World Health Organization officially names the disease as COVID-19.1 The new coronavirus is highly contagious. The rapid spread of SARS-CoV-2 lead to declare the pandemic on the 11th March 2020. On 10 May 2020 the number of infected people is 4,132,373 worldwide.2 This article is protected by copyright. All rights reserved.
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Métodos de diagnóstico rápido de las infecciones respiratorias
Acute respiratory infections are the second cause of morbidity and mortality in children and adults worldwide, being viruses, bacteria and fungi involved in their etiology. The rapid diagnosis allows for a better clinical management of the patient, for adopting public health measures and for controlling possible outbreaks. The main etiologic agents can be diagnosed within the first hours after the onset of symptoms with antigen detection techniques, primarily immunochromatography. Results are obtained in 15–30 minutes, with 70–90% sensitivity and >95% specificity for the diagnosis of Streptococcus pneumoniae and Legionella pneumophila serogroup O1 infections from urine, Streptococcus pyogenes from throat swabs and respiratory syncytial virus from nasopharyngeal aspirates. Worse results are obtained for influenza viruses and Pneumocystis jirovecii with these techniques; however, other easy-to-perform molecular techniques are available for the rapid diagnosis of these microorganisms. In general, these techniques should not be used for monitoring the outcome or response to treatment.
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Assessment of air purifier on efficient removal of airborne bacteria, Staphylococcus epidermidis, using single-chamber method
We evaluated the efficiency of an air purifier using the single-chamber method for the effective removal of airborne Staphylococcus epidermidis, a nosocomial infection–causing bacterium. In this experiment, the bacterial strain S. epidermidis was injected using a nebulizer into the test chamber, which was similar to a consumer living space (60 m(3)). The microbial sampling was conducted via the air sampler method, and the reduction in S. epidermidis growth was monitored by performing three consecutive tests. Initially, a blank test was conducted to determine the natural decay rate and calibrate the experimental setup. After injecting the bacterial strain from 1240 to 11180 CFU per unit volume (m(3)), the natural decay rate showed a maximum deviation of 3.1% with a sampling error of 1.1% p at a confidence level of 95%. In addition, the particle size distribution in the test chamber was found to range from 0.3 to 5.0 μm, and a subsequent decrease in large-sized particles was observed with the operation of the air purifier, which is the size similar to that of suspended airborne bacteria. This can be used to assess the performance of the air purifier by calibrating the natural reduction value to the reduced operation value. Thus, the single-chamber technique is a promising approach for analyzing the removal efficacy of airborne bacteria from indoor air.
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Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review
In the last years, consumers are paying much more attention to natural medicines and principles, mainly due to the general sense that natural compounds are safe. On the other hand, there is a growing demand by industry for plants used in traditional medicine that could be incorporated in foods, nutraceuticals, cosmetics, or even pharmaceuticals. Glycyrrhiza glabra Linn. belongs to the Fabaceae family and has been recognized since ancient times for its ethnopharmacological values. This plant contains different phytocompounds, such as glycyrrhizin, 18β‐glycyrrhetinic acid, glabrin A and B, and isoflavones, that have demonstrated various pharmacological activities. Pharmacological experiments have demonstrated that different extracts and pure compounds from this species exhibit a broad range of biological properties, including antibacterial, anti‐inflammatory, antiviral, antioxidant, and antidiabetic activities. A few toxicological studies have reported some concerns. This review addresses all those issues and focuses on the pharmacological activities reported for G. glabra. Therefore, an updated, critical, and extensive overview on the current knowledge of G. glabra composition and biological activities is provided here in order to explore its therapeutic potential and future challenges to be utilized for the formulation of new products that will contribute to human well‐being.
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Cutaneous involvement during COVID‐19 pandemic: an emerging sign of infection
Since December 2019, SARS‐CoV‐2 epidemic has spread all over the world.(1) To date, few reports regarding the cutaneous involvement in COVID‐19 have been published.(2,3) Herein, we report a four cases series describing skin lesions probably related with COVID‐19. The case 1 was a 66‐year‐old Caucasian female with a history of hypertension and dyslipidaemia. When hospitalized, she showed fever, nasal congestion and pneumonia symptoms. A chest‐TC displayed bilateral interstitial lungs’ involvement and a nasopharyngeal‐swab confirmed SARS‐CoV‐2 infection. At day 6 of hospitalization, an asymptomatic erythematous‐pomphoid skin rash occurred on the trunk (Figure 1A).
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COVID-19 Pandemic and Cardiac Electrophysiology: Guidance Protocol From a UK Tertiary Cardiac Center
Since December 2019, the COVID-19 pandemic has resulted in more than 2,160,000 positive cases and more than 145,000 deaths until April 18, 2020. The pressure to the health services worldwide has been unprecedented. The redeployment of staff and resources to treat more efficiently COVID-19 cases along with the need to reduce disease transmission has affected the field of electrophysiology among many others. Amendments to clinical pathways are obligatory in this perspective to continue to provide the necessary health services to the people who need them, although at the same time, infection control and prevention are not compromised by inadvertent disease transmission or unnecessary use of resources. We aim to provide a guide of the logistic aspects of electrophysiology procedures derived from our tertiary cardiac center during the current COVID-19 pandemic.
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Follow-up for pregnant women during the COVID-19 pandemic: French national authority for health recommendations
INTRODUCTION: In the context of the stage 3 SARS-Cov-2 epidemic situation, it is necessary to put forward a method of rapid response for an HAS position statement in order to answer to the requests from the French Ministry of Solidarity and Health, healthcare professionals and/or health system users’ associations concerning follow-up of pregnant women during the COVID-19 outbreak. METHODS: A simplified 7-step process that favours HAS collaboration with experts (healthcare professionals, health system users’ associations, scientific societies etc.), the restrictive selection of available evidence and the use of digital means of communication. A short and specific dissemination format, which can be quickly updated in view of the changes in available data has been chosen.
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Systemic isotretinoin therapy in the era of COVID‐19
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Appealing for efficient, well organized clinical trials on COVID-19.
Background The rapid emergence of clinical trials on COVID-19 stimulated a wave of discussion in scientific community. It is important to understand the characteristics of the ongoing or pending interventional clinical trials on COVID-19. Methods We reviewed the characteristics of interventional trials from Chinese Clinical Trial Registration (ChiCTR) and ClinicalTrials.gov. A total of 171 COVID-19-related interventional trials were identified on Feb 22, 2020. These trials are classified into 4 categories based on treatment modalities, including chemical drugs (CDs), biological therapies (BTs), traditional Chinese medicine (TCM) treatments and other therapies. Results Our analysis focused on the issues of stage, design, randomization, blinding, primary endpoints (PEs) definition and sample size of these trials. Although most trials use parallel-arm design (88.3%) and randomization (77.2%), blinding is applied in only 25 trials (14.6%). More than half of the trials planned to recruit ≤100 patients, indicating a possibility of insufficient statistical power. About one third of trials will recruit severe and critically ill patients. More trials on traditional Chinese medical treatment use 2 or more PEs than those on CDs or biological treatments (57.6%, 39.4% and 40.5%, respectively). Conclusions We found some studies with potential defects including unreasonable design, inappropriate PE and small sample size. Clinical trials on COVID-19 should be designed based on scientific rules, ethics and benefits for patients.
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Atypical presentation of SARS-CoV-2 infection: A case report.
BACKGROUND The first case of pneumonia subsequently attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, Hubei Province on December 8, 2019. The symptoms included fever, coughing, and breathing difficulties. A few patients with this infection may only have atypical symptoms, which could lead to a misdiagnosis and subsequently further facilitate the spread of the virus. CASE SUMMARY A 74-year-old female patient complained of severe diarrhea. She did not have fever, coughing, or breathing difficulties. A physical examination revealed no obvious positive signs. The patient had been hypertensive for more than 10 years. Her blood pressure was well controlled. On January 9, 2020, the patient's son visited a colleague who was later confirmed positive for SARS-CoV-2 and his first close contact with our patient was on January 17. The patient was first diagnosed with gastrointestinal dysfunction. However, considering her indirect contact with a SARS-CoV-2-infected individual, we suggested that an atypical pneumonia virus infection should be ruled out. A computed tomography scan was performed on January 26, and showed ground-glass nodules scattered along the two lungs, suggestive of viral pneumonia. Given the clinical characteristics, epidemiological history, and examination, the patient was diagnosed with coronavirus disease-2019 (COVID-19). CONCLUSION Our patient had atypical symptoms of COVID-19. Careful acquisition of an epidemiological history is necessary to make a correct diagnosis and strategize a treatment plan.
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Synthesis, antitubercular and anticancer activity of new Baylis–Hillman adduct-derived N-cinnamyl-substituted isatin derivatives
Baylis–Hillman adduct-derived N-cinnamyl-substituted isatin derivatives were synthesized and evaluated for their antitubercular activity on Mycobacterium tuberculosis H(37)Rv strain ATCC 27294 by agar dilution method. Anticancer activity for the same compounds was also screened on four different cell lines: Chinese hamster ovary (CHO cells), Colo 205 (human colon cancer), Sup-T1 (human lymphoma) and C6 glioma (rat glioma) by MTT assay method. The compounds (3j–l) have shown significant activity against Mycobacterium strain and the compound 3l has shown specific cytotoxic activity.
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SeMet attenuates OTA-induced PCV2 replication promotion by inhibiting autophagy by activating the AKT/mTOR signaling pathway
Porcine circovirus type 2 (PCV2) is recognized as the causative agent of porcine circovirus-associated diseases. PCV2 replication could be promoted by low doses of ochratoxin A (OTA) as in our previous study and selenium has been shown to attenuate PCV2 replication. However, the underlying mechanism remains unclear. The aim of the study was to investigate the effects of selenomethionine (SeMet), the major component of organic selenium, on OTA-induced PCV2 replication promotion and its potential mechanism. The present study demonstrates that OTA could promote PCV2 replication as measured by cap protein expression, viral titer, viral DNA copies and the number of infected cells. In addition, OTA could activate autophagy as indicated by up-regulated light chain 3 (LC3)-II and autophagy-related protein 5 expressions and autophagosome formation. Further, OTA could down-regulate p-AKT and p-mTOR expressions and OTA-induced autophagy was inhibited when insulin was applied. SeMet at 2, 4 and 6 μM had significant inhibiting effects against OTA-induced PCV2 replication promotion. Furthermore, SeMet could attenuate OTA-induced autophagy and up-regulate OTA-induced p-AKT and p-mTOR expression inhibition. Rapamycin, an inhibitor of AKT/mTOR, could reverse the effects of SeMet on OTA-induced autophagy and the PCV2 replication promotion. In conclusion, SeMet could block OTA-induced PCV2 replication promotion by inhibiting autophagy by activating the AKT/mTOR pathway. Therefore, SeMet supplementation could be an effective prophylactic strategy against PCV2 infections and autophagy may be a potential marker to develop novel anti-PCV2 drugs.
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Safeguarding Dermatologist Attendings and Residents Amid the COVID‐19 Pandemic: Focus on Special Populations
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Evolution of a Search: The Use of Dynamic Twitter Searches During Superstorm Sandy
Background: Twitter has emerged as a critical source of free and openly available information during emergency response operations, providing an unmatched level of on-the-ground situational awareness in real-time. Responders and survivors turn to Twitter to share information and resources within communities, conduct rumor control, and provide a “boots on the ground” understanding of the disaster. However, the ability to tune out background “noise” is essential to effectively utilizing Twitter to identify important and useful information during an emergency response. Methods: This article highlights a two-prong strategy in which the use of a Twitter list paired with subject specific Boolean searches provided increased situational awareness and early event detection during the United States Department of Health and Human Services (HHS), Office of the Assistant Secretary for Preparedness and Response (ASPR) response to Superstorm Sandy in 2012. To maximize the amount of relevant information that was retrieved, the Twitter list and Boolean searches were dynamic and responsive to real-time developments, evolving health threats, and the informational needs of decision-makers. Conclusion: The use of a Twitter list combined with Boolean searches led to enhanced situational awareness throughout the HHS response. The incorporation of a dynamic search strategy over the course of the HHS Sandy response, allowed for the ability to account for over-tweeted information, changes in event related conversation, and decreases in the return of relevant information.
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Measuring inequalities in the public health workforce at county-level Centers for Disease Control and Prevention in China
BACKGROUND: The public health workforce (PHW) is a key component of a country’s public health system. Since the outbreak of SARS (severe acute respiratory syndrome) in 2003, the scale of PHW in China has been continuously expanding, but policymakers and researchers still focus on the distribution of public health personnel, especially the regional inequality in such distribution. We aimed to identify the root cause of PHW inequality by decomposing different geographical units in China. METHODS: This study was based on data from a nationwide survey, which included 2712 county-level data. The distribution of the PHW in geographical units was evaluated by the Gini coefficient and Theil T index, and inequalities at regional, provincial, and municipal levels were decomposed to identify the root causes of inequalities in the PHW. Additionally, the contextual factors affecting the distribution of the PHW were determined through regression analysis. RESULTS: The overall inequality results show that health professional and field epidemiological investigators faced worse inequality than the staff. In particular, field epidemiological investigators had a Gini coefficient close to 0.4. Step decomposition showed that within-region inequalities accounted for 98.5% or more of overall inter-county inequality in the distribution of all PHW categories; provincial decomposition showed that at least 74% of inequality is still distributed within provinces; the overall contribution of within-municipal inequality and between-municipal inequality was basically the same. Further, the contextual factor that influenced between-municipality and within-municipality inequality for all three categories of PHWs was the agency building area per employee. Per capita GDP had a similar effect, except for between-municipality inequality of professionals and within-municipality inequality of field epidemiological investigators. CONCLUSIONS: The successive decomposition showed that inequality is mainly concentrated in counties at the within-province and within-municipal levels. This study clearly suggests that the government, especially the municipal government at the provincial level, should increase financial investment in Centers for Disease Control and Prevention (CDCs) with worse resource allocation in their jurisdiction through various ways of compensation and incentives, enhance their infrastructure, and improve the salary of personnel in these institutions, to attract more public health professionals to these institutions.
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Covid-19 and lung cancer: A greater fatality rate?
BACKGROUND: Currently there are no reported series determining the Covid-19 infected lung cancer patient´s characteristics and outcome that allow us to clarify strategies to protect our patients. In our study we determine whether exists differences in cumulative incidence and severity of Covid-19 infection between lung cancer patients visiting our Medical Oncology department and the reference population of our center (320,000 people), in the current epicenter of the pandemic in Europe (Madrid, Spain). We also describe clinical and demographic factors associated with poor prognosis and Covid-19 treatment outcomes. PATIENTS AND METHODS: We retrospectively reviewed 1878 medical records of all Covid-19 patients who were admitted at Hospital Universitario Infanta Leonor of Madrid between March 5, 2020 and April 7, 2020, in order to detect cumulative incidence of Covid-19 in lung cancer patients. We also described Covid-19 treatment outcome, mortality and associated risk factors using univariate and multivariate logistic regression analysis. RESULTS: 17/1878 total diagnosis in our center had lung cancer (0.9%) versus 1878/320,000 of the total reference population (p = 0.09). 9/17 lung cancer patients with Covid-19 diagnosis died (52.3%) versus 192/1878 Covid-19 patients in our center (p<0.0001). Dead lung cancer patients were elderly compared to survivors: 72 versus 64.5 years old (p = 0.12). Combined treatment with hydroxychloroquine and azithromycin improves the outcome of Covid-19 in lung cancer patients, detecting only 1/6 deaths between patients under this treatment versus others treatment, with statistical significance in the univariate and multivariate logistic regression (OR 0.04, p = 0.018). CONCLUSIONS: Lung cancer patients have a higher mortality rate than general population. Combined hydroxychloroquine and azithromycin treatment seems like a good treatment option. It is important to try to minimize visits to hospitals (without removing their active treatments) in order to decrease nosocomial transmission.
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Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms: An Analysis of Seven Patients in China
Objectives: Patients with novel coronavirus disease 2019 (COVID-19) can present with gastrointestinal symptoms as their initial symptoms or as the main manifestations during disease progression, but the clinical characteristics of these patients are still unknown. Methods: We identified COVID-19 patients who admitted to Xiangyang No. 1 People's Hospital and presented with gastrointestinal symptoms as their initial or main symptoms. Their medical records were reviewed by two independent clinical scientists. The epidemiological and clinical characteristics as well as the clinical outcomes were analyzed. Results: Among 142 confirmed COVID-19 cases, 7 (4.9%) of them presented with gastrointestinal symptoms. Three patients had gastrointestinal symptoms as the initial symptoms and chief complaints, and 4 patients as the main symptoms during disease progression. Six patients had symptoms of diarrhea (3–16 days), 7 with anorexia (7–22 days), 6 with upper abdominal discomfort (1–7 days), and 4 with nausea (1–7 days), 1 with heartburn lasting 2 days, and 2 with vomiting symptoms (1 day). The chest CT scan showed typical COVID-19 imaging features, and associated with the progression of the disease. During treatment, 2 patients died due to organ failure. Discussion: COVID-19 patients with gastrointestinal symptoms are relatively rare and might be misdiagnosed. The clinical features include watery stools, anorexia, and upper abdominal discomfort. These patients may have severe disease and be associated with a poor prognosis. The underlying mechanisms of SARS-CoV-2 related gastrointestinal symptoms need to clarify in future studies.
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Increased Flavonoid Compounds from Fermented Houttuynia cordata using Isolated Six of Bacillus from Traditionally Fermented Houttuynia cordata
Flavonoids, which form a major component in Houttuynia cordata Thunb., display a wide range of pharmacological activities. The expression of plant flavonoids is partly regulated by fermentation. Therefore, we studied the effects of fermentation on H. cordata in order to identify the strains present during the fermentation process, and to determine whether fermented H. cordata could be used as a probiotic. Our results showed that all 6 of the bacterial strains isolated from fermented H. cordata (FHC) belonged to the genus Bacillus. As expected, fermenting H cordata also increased the flavonoid content as increases were observed in the levels of rutin, quercitrin, and quercetin. To test the effects of fermentation, we treated LPS-stimulated RAW264.7 cells with non-fermented H. cordata extracts (HCE) or FHC extracts (FHCE). Compared to the HCE-treated cells, the FHCE-treated cells showed increased viability. No cytotoxic effects were detected in the FHCE-treated groups in the 2 cell lines used in the study, namely, RAW264.7 and RBL-2H3. FHCE-treated HepG2 cells showed decreased growth, compared to HCE-treated HepG2 cells. These results indicate that the fermented H. cordata predominantly contained Bacillus strains. Furthermore, FHCE are able to prevent LPS-induced inflammatory effects and inhibit the growth of HepG2 cells.
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The Story behind COVID-19: Animal Diseases at the Crossroads of Wildlife, Livestock and Human Health
A number of virological, epidemiological and ethnographic arguments suggest that COVID-19 has a zoonotic origin. The pangolin, a species threatened with extinction due to poaching for both culinary purposes and traditional Chinese pharmacopoeia, is now suspected of being the “missing link” in the transmission to humans of a virus that probably originated in a species of bat. Our predation of wild fauna and the reduction in their habitats have thus ended up creating new interfaces that favour the transmission of pathogens (mainly viruses) to humans. Domesticated animals and wild fauna thus constitute a reservoir for almost 80% of emerging human diseases (SARS-CoV, MERS-CoV, Ebola). These diseases are all zoonotic in origin. As if out of a Chinese fairy tale, the bat and the pangolin have taught us a lesson: within an increasingly interdependent world, environmental crises will become ever more intertwined with health crises. Questions relating to public health will no longer be confined to the secrecy of the physician’s consulting room or the sanitised environment of the hospital. They are now being played out in the arena of international trade, ports and airports and distribution networks. Simply put, all human activity creates new interfaces that facilitate the transmission of pathogens from an animal reservoir to humans. This pluri-disciplinary article highlights that environmental changes, such as the reduction in habitats for wild fauna and the intemperate trade in fauna, are the biggest causes of the emergence of new diseases. Against this background, it reviews the different measures taken to control, eradicate and prevent the emergence of animal diseases in a globalised world.
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COVID-19 causes unprecedented educational disruption: Is there a road towards a new normal?
COVID-19 confronts the education system with a new and massive crisis. What should a “new normal” look like for future generations? How can countries use the innovativeness of the recovery period to “build back better”? This Viewpoint highlights the UNESCO-led Global Coalition for Education initiative, which is seeking solutions to support learners and teachers, as well as governments throughout the recovery process, with a principal focus on inclusion, equity, and gender equality. The Viewpoint also argues that the current crisis is an opportunity for stronger international collaboration, which might provide a better focus and deliver solutions, including digital tools. Resilience and adaptability will be crucial for the next generations to navigate through the present—and any future—pandemic.