title: Möglichkeiten der Beschäftigung von schwangeren Mitarbeiterinnen im Gesundheitssystem in Zusammenhang mit SARS-CoV-2

text: Continued employment of pregnant women related to COVID (Corona Virus Disease) should only be considered if the risk of infection in the workplace is not higher than that of the general population. This option should therefore be carried out after an individual risk assessment with a precise description of the patient clientele and definition of the activities to be performed.


title: Nanoparticles for Signaling in Biodiagnosis and Treatment of Infectious Diseases

text: Advances in nanoparticle-based systems constitute a promising research area with important implications for the treatment of bacterial infections, especially against multidrug resistant strains and bacterial biofilms. Nanosystems may be useful for the diagnosis and treatment of viral and fungal infections. Commercial diagnostic tests based on nanosystems are currently available. Different methodologies based on nanoparticles (NPs) have been developed to detect specific agents or to distinguish between Gram-positive and Gram-negative microorganisms. Also, biosensors based on nanoparticles have been applied in viral detection to improve available analytical techniques. Several point-of-care (POC) assays have been proposed that can offer results faster, easier and at lower cost than conventional techniques and can even be used in remote regions for viral diagnosis. Nanoparticles functionalized with specific molecules may modulate pharmacokinetic targeting recognition and increase anti-infective efficacy. Quorum sensing is a stimuli-response chemical communication process correlated with population density that bacteria use to regulate biofilm formation. Disabling it is an emerging approach for combating its pathogenicity. Natural or synthetic inhibitors may act as antibiofilm agents and be useful for treating multi-drug resistant bacteria. Nanostructured materials that interfere with signal molecules involved in biofilm growth have been developed for the control of infections associated with biofilm-associated infections.


title: Molecular detection of respiratory viruses in immunocopromised ICU patients: Incidence and meaning

text: Summary Purpose Prospective single-center study to assess the sensitivity and clinical relevance of molecular testing for respiratory viruses in critically ill immunocompromised patients with acute respiratory failure (ARF). Methods 100 consecutive critically ill immunocompromised patients with ARF in 2007–2009. Among them, 65 had hematologic malignancies (including 14 hematopoietic stem cell transplant recipients), 22 had iatrogenic immunosuppression, and 13 had solid malignancies. A multiplex molecular assay (MMA) was added to the usual battery of tests performed to look for causes of ARF. Results Nasopharyngeal aspirates and/or bronchoalveolar lavage fluid were tested for respiratory viruses using both the MMA and immunofluorescence. A virus was detected in 47 (47%) patients using the MMA and 8 (8%) patients using immunofluorescence (P = 0.006). MMA-positive and MMA-negative patients had similar clinical and radiographic presentations and were not significantly different for the use of ventilatory support (58% vs. 76%, P = 0.09), occurrence of shock (43% vs. 53%, P = 0.41), use of renal replacement therapy (26% vs. 23%, P = 0.92), SAPS II (35 [26–44] vs. 38 [27–50], P = 0.36), time spent in the ICU (6 vs. 7 days, P = 0.35), or ICU mortality (17% vs. 28%, P = 0.27). Using MMA, a virus was found in 6 of the 12 patients with no diagnosis at the end of the etiologic investigations. Conclusions In critically ill immunocompromised patients, an MMA was far more sensitive than immunofluorescence for respiratory virus detection. Patients with RVs detected in the respiratory tract had the same clinical characteristics and outcomes as other patients.


title: Antimicrobial Resistance Determinants and Future Control

text: At the beginning of the 21st century, antimicrobial resistance is common, has developed against every class of antimicrobial drug, and appears to be spreading into new clinical niches. We describe determinants likely to influence the future epidemiology and health impact of antimicrobial-resistant infections. Understanding these factors will ultimately optimize preventive strategies for an unpredictable future.


title: Estimating and Projecting Air Passenger Traffic during the COVID-19 Coronavirus Outbreak and its Socio-Economic Impact

text: Abstract Due to the coronavirus global crisis, most countries have put in place restrictive measures in order to confine the pandemia and contain the number of casualties. Among the restrictive measures, air traffic suspension is certainly quite effective in reducing the mobility on the global scale in the short term but it also has high socio-economic impact on the long and short term. The main focus of this study is to collect and prepare data on air passengers traffic worldwide with the scope of analyze the impact of travel ban on the aviation sector. Based on historical data from January 2010 till October 2019, a forecasting model is implemented in order to set a reference baseline. Making use of airplane movements extracted from online flight tracking platforms and on-line booking systems, this study presents also a first assessment of recent changes in flight activity around the world as a result of the COVID-19 pandemic. To study the effects of air travel ban on aviation and in turn its socio-economic, several scenarios are constructed based on past pandemic crisis and the observed flight volumes. It turns out that, according to these hypothetical scenarios, in the first Quarter of 2020 the impact of aviation losses could have negatively reduced World GDP by 0.02% to 0.12% according to the observed data and, in the worst case scenarios, at the end of 2020 the loss could be as high as 1.41-1.67% and job losses may reach the value of 25-30 millions. Focusing on EU27, the GDP loss may amount to 1.66-1.98% by the end of 2020 and the number of job losses from 4.2 to 5 millions in the worst case scenarios. Some countries will be more affected than others in the short run and most European airlines companies will suffer from the travel ban. We hope that that these preliminary results may be of help for informed policy making design of exit strategies from this global crisis.


On viral epidemics, zoonoses and memory


docid: mauzesor

title: Quasispecies and the implications for virus persistence and escape

text: Abstract Background: In the 1970s Manfred Eigen and colleagues proposed a new model of molecular evolution to explain adaptability and rapid evolution of simple replicons, as those that probably populated the earth at the onset of life. This model of evolution placed emphasis on mutant generation, to the point of invalidating the concept of wild-type genomes as a defined sequence of nucleotides. In striking similarity with the proposals for such early replicons, present-day RNA viruses consist of complex distributions of nonidentical but closely related genomes termed quasispecies. Objectives: To discuss indeterminations inherent to a quasispecies structure and to the analytical procedures to define it, biological implications of quasispecies, and the need to take into account this type of population structure, in order to design effective strategies to prevent and control diseases caused by highly variable viruses. Results: Quasispecies have many biological implications, extending from viral pathogenesis to the emergence of new pathogens, rapid antigenic variation, and alterations in cell tropism, virulence, host range and viral gene expression. Conclusions: Diseases caused by highly variable RNA viruses prove very difficult to control and vaccine development against such viruses are largely unsuccessful. It is important to understand quasispecies composition and dynamics, as quasispecies are an important step in the natural history of RNA viruses.


title: Collaborative Cross Mice Yield Genetic Modifiers for Pseudomonas aeruginosa Infection in Human Lung Disease

text: Human genetics influence a range of pathological and clinical phenotypes in respiratory infections; however, the contributions of disease modifiers remain underappreciated. We exploited the Collaborative Cross (CC) mouse genetic-reference population to map genetic modifiers that affect the severity of Pseudomonas aeruginosa lung infection. Screening for P. aeruginosa respiratory infection in a cohort of 39 CC lines exhibits distinct disease phenotypes ranging from complete resistance to lethal disease. Based on major changes in the survival times, a quantitative-trait locus (QTL) was mapped on murine chromosome 3 to the genomic interval of Mb 110.4 to 120.5. Within this locus, composed of 31 protein-coding genes, two candidate genes, namely, dihydropyrimidine dehydrogenase (Dpyd) and sphingosine-1-phosphate receptor 1 (S1pr1), were identified according to the level of genome-wide significance and disease gene prioritization. Functional validation of the S1pr1 gene by pharmacological targeting in C57BL/6NCrl mice confirmed its relevance in P. aeruginosa pathophysiology. However, in a cohort of Canadian patients with cystic fibrosis (CF) disease, regional genetic-association analysis of the syntenic human locus on chromosome 1 (Mb 97.0 to 105.0) identified two single-nucleotide polymorphisms (rs10875080 and rs11582736) annotated to the Dpyd gene that were significantly associated with age at first P. aeruginosa infection. Thus, there is evidence that both genes might be implicated in this disease. Our results demonstrate that the discovery of murine modifier loci may generate information that is relevant to human disease progression.


title: Investigation on ultrasound assisted extraction of saikosaponins from Radix Bupleuri

text: Abstract Ultrasound assisted extraction (UAE) of saikosaponins from Radix Bupleuri (Bupleurum Chinense DC) was studied. The effects of various factors such as time (t), temperature (T), ultrasound power (I), particle size (S), solvent to solid ratio (R) and solvent concentration (C) on the yield of target components were investigated. The experimental results indicated that the extraction by UAE is six times faster than those by conventional thermal extraction. It is also found that fast extraction rate was obtained in the first 30min of sonication. Prolonged sonication did not give a proportional increase in the yield. For the effect of ultrasound power, the maximum yield was obtained at the power level of around 21W. Scanning electron microscope (SEM) images of the plant cells after UAE treatment were obtained to provide visual evidence of the sonication effect. The effects of particle size, solvent to solid ratio and solvent concentration on the yield are also discussed. The preliminary optimum conditions for UAE of saikosaponins were found at time of 30min, temperature of 80°C, power of 21W, particle size <0.3mm, solvent to solid ratio of 25ml/g and solvent concentration of 50%.


docid: jlwctmxw

title: Bacteria emitted in ambient air during bronchoscopy—a risk to health care workers?

text: BACKGROUND: Health care workers are at risk of occupational infections, and some procedures are known to increase this risk. The aim of this study was to qualify and quantify bioaerosol concentrations during bronchoscopy to estimate the occupational risk. METHODS: Full-day sampling was conducted in 2 rooms while bronchoscopies were performed on patients. Two microbial air samplers were used, a wet wall cyclonic sampler and an impactor, on culture media. Identification of the culturable bacterial flora was performed with chromatographic analysis of cellular fatty acid of the isolated strain and additional biochemical tests if needed. Specific polymerase chain reaction analysis was completed on wet wall cyclonic samples for the detection of influenza A and B and Mycobacterium spp. RESULTS: A wide variety of bacteria were collected from the ambient air. All samples yielded at least 1 Staphylococcus species. Although most of the culturable bacteria identified were normal nonpathogenic flora, such as Streptococcus spp, Neisseria spp, and Corynebacterium spp, some opportunistic pathogens, such as Streptococcus pneumoniae, were found. Neither Mycobacterium spp nor influenza virus was detected with the polymerase chain reaction method during this study. CONCLUSIONS: Culturable bacteria from oral, nasal, and pulmonary flora are aerosolized during bronchoscopy and could be inhaled by medical staff. The potential presence of pathogens in those aerosols could represent an occupational infection risk.


title: De novo Sequence Assembly and Characterization of Lycoris aurea Transcriptome Using GS FLX Titanium Platform of 454 Pyrosequencing

text: BACKGROUND: Lycoris aurea, also called Golden Magic Lily, is an ornamentally and medicinally important species of the Amaryllidaceae family. To date, the sequencing of its whole genome is unavailable as a non-model organism. Transcriptomic information is also scarce for this species. In this study, we performed de novo transcriptome sequencing to produce the first comprehensive expressed sequence tag (EST) dataset for L. aurea using high-throughput sequencing technology. METHODOLOGY AND PRINCIPAL FINDINGS: Total RNA was isolated from leaves with sodium nitroprusside (SNP), salicylic acid (SA), or methyl jasmonate (MeJA) treatment, stems, and flowers at the bud, blooming, and wilting stages. Equal quantities of RNA from each tissue and stage were pooled to construct a cDNA library. Using 454 pyrosequencing technology, a total of 937,990 high quality reads (308.63 Mb) with an average read length of 329 bp were generated. Clustering and assembly of these reads produced a non-redundant set of 141,111 unique sequences, comprising 24,604 contigs and 116,507 singletons. All of the unique sequences were involved in the biological process, cellular component and molecular function categories by GO analysis. Potential genes and their functions were predicted by KEGG pathway mapping and COG analysis. Based on our sequence analysis and published literatures, many putative genes involved in Amaryllidaceae alkaloids synthesis, including PAL, TYDC OMT, NMT, P450, and other potentially important candidate genes, were identified for the first time in this Lycoris. Furthermore, 6,386 SSRs and 18,107 high-confidence SNPs were identified in this EST dataset. CONCLUSIONS: The transcriptome provides an invaluable new data for a functional genomics resource and future biological research in L. aurea. The molecular markers identified in this study will provide a material basis for future genetic linkage and quantitative trait loci analyses, and will provide useful information for functional genomic research in future.


title: CDC42 Use in Viral Cell Entry Processes by RNA Viruses

text: The cellular actin cytoskeleton presents a barrier that must be overcome by many viruses, and it has become increasingly apparent many viral species have developed a diverse repertoire of mechanisms to hijack cellular actin-regulating signalling pathways as part of their cell entry processes. The Rho family GTPase Cdc42 is appreciated as a key moderator of cellular actin dynamics, and the development of specific Cdc42-inhibiting agents has given us an unprecedented ability to investigate its individual role in signalling pathways. However, investigative use of said agents, and the subsequent characterisation of the role Cdc42 plays in viral entry processes has been lacking. Here, we describe the current literature on the role of Cdc42 in human immunodeficiency virus (HIV)-1 cell entry, which represents the most investigated instance of Cdc42 function in viral cell entry processes, and also review evidence of Cdc42 use in other RNA virus cell entries, demonstrating prime areas for more extensive research using similar techniques.


The future of biological warfare


Lung herniation mimicking COVID-19


title: Genetic and antigenic characterization of recombinant nucleocapsid proteins derived from canine coronavirus and canine respiratory coronavirus in China

text: To characterize the antigenicity of nucleocapsid proteins (NP) derived from canine coronavirus (CCoV) and canine respiratory coronavirus (CRCoV) in China, the N genes of CCoV (CCoV-BJ70) and CRCoV (CRCoV-BJ202) were cloned from swabs obtained from diseased pet dogs in Beijing and then sequenced. The recombinant NPs (rNPs) were expressed in Escherichia coli and purified by nickel-affinity column and size exclusion chromatography. Sequencing data indicated that the N genes of CCoV-BJ70 and CRCoV-BJ202 belonging to two distinctly different groups were relatively conserved within each subgroup. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results showed that rNPs of CCoV and CRCoV were expressed efficiently and isolated with a final purity of over 95%. Western blot analysis revealed the rNP from CRCoV could cross-react with mice antisera against human coronavirus (HCoV-229E, NL63, OC43, HKU1), while rNP of CCoV had cross-reactivity with only anti-sera against viruses belonging to the same group (HCoV-229E and NL63). In summary, CCoV and CRCoV rNPs were successfully expressed in E. coli and showed antigenic cross-reactivity with antisera raised against human coronaviruses. These findings indicate that further serologic studies on coronavirus infections at the animal-human interface are needed.


title: Rapid Sentinel Surveillance for COVID-19 — Santa Clara County, California, March 2020

text: On February 27, 2020, the Santa Clara County Public Health Department (SCCPHD) identified its first case of coronavirus disease 2019 (COVID-19) associated with probable community transmission (i.e., infection among persons without a known exposure by travel or close contact with a patient with confirmed COVID-19). At the time the investigation began, testing guidance recommended focusing on persons with clinical findings of lower respiratory illness and travel to an affected area or an epidemiologic link to a laboratory-confirmed COVID-19 case, or on persons hospitalized for severe respiratory disease and no alternative diagnosis (1). To rapidly understand the extent of COVID-19 in the community, SCCPHD, the California Department of Public Health (CDPH), and CDC began sentinel surveillance in Santa Clara County. During March 5-14, 2020, four urgent care centers in Santa Clara County participated as sentinel sites. For this investigation, county residents evaluated for respiratory symptoms (e.g., fever, cough, or shortness of breath) who had no known risk for COVID-19 were identified at participating urgent care centers. A convenience sample of specimens that tested negative for influenza virus was tested for SARS-CoV-2 RNA. Among 226 patients who met the inclusion criteria, 23% had positive test results for influenza. Among patients who had negative test results for influenza, 79 specimens were tested for SARS-CoV-2, and 11% had evidence of infection. This sentinel surveillance system helped confirm community transmission of SARS-CoV-2 in Santa Clara County. As a result of these data and an increasing number of cases with no known source of transmission, the county initiated a series of community mitigation strategies. Detection of community transmission is critical for informing response activities, including testing criteria, quarantine guidance, investigation protocols, and community mitigation measures (2). Sentinel surveillance in outpatient settings and emergency departments, implemented together with hospital-based surveillance, mortality surveillance, and serologic surveys, can provide a robust approach to monitor the epidemiology of COVID-19.


title: Successful Anesthetic Management in Cesarean Section for Pregnant Woman with COVID-19

text: Patient: Female, 29-year-old Final Diagnosis: COVID-19 Symptoms: Pregnancy Medication: — Clinical Procedure: Cesarian section • spinal anesthesia Specialty: Anesthesiology OBJECTIVE: Unusual setting of medical care BACKGROUND: The current COVID-19 pandemic highlights the importance of the mindful use of financial and human resources. Preventing infections and preserving resources and manpower are crucial in healthcare. It is important to ensure the ability of surgeons and specialized interventionalists to function through the pandemic. Until now, no justified protocol has been reported for the anesthetic management in cesarean section (CS). CASE REPORT: A 29-year-old pregnant woman, G2P1 at 37+4 weeks of gestation, was referred to our center on March 28, 2020, after she had tested positive for COVID-19. She was stable and the CS was planned after she reached term. Through spinal anesthesia, CS was conducted. The anesthesia team was protected with full personal protection equipment. The operation was carried out smoothly without complication. A female neonate was delivered and was tested to be negative for COVID-19. No medical staff cross-infection was reported. CONCLUSIONS: Special precautions should be considered when pregnant women are undergoing CS. Spinal anesthesia is preferred over general anesthesia.


title: Effect of prebiotic supplementation with stabilized rice bran in milk of pre-weaned organic Holstein calves

text: BACKGROUND: The first month of life possess significant challenges for dairy calves due to high susceptibility to digestive diseases. The objective of this study was to evaluate the effect of prebiotic supplementation with stabilized rice bran (SRB) in milk on health, immunity, and performance of pre-weaned organic dairy calves. Holstein heifer calves (n = 90) were enrolled at 6 ± 1 days old and monitored for 28 days, from July to August 2017. Calves were randomly assigned to a control (CTR; n = 45) or a treatment group (SRB; n = 45). The CTR group received milk alone and the SRB group received 120 g of SRB per day in milk to achieve a 10% w/w dose of the total calories. Daily health evaluations were conducted to score health status and disease severity (healthy, slightly affected, moderately or severely sick) of calves, through integrated assessment of diarrhea, dehydration, attitude, and milk intake. Body weights and fecal IgA quantification were completed on the first and last day of the study. RESULTS: Overall, weight gain and fecal IgA concentrations were not affected by the dietary addition of SRB. The total number of calf-days classified as healthy or sick were not different between treatment groups. Similarly, the number of calf-days categorized as slightly affected, moderately sick, or severely sick did not differ between treatment groups. Time to event analyses indicated a tendency for a treatment effect in the time to the first moderate case of diarrhea (P = 0.08), as well as in the time to recovery from diarrhea (P = 0.052), favoring control calves. CONCLUSIONS: These results indicated that the dietary addition of SRB in milk did not have an effect in health, immunity or performance of pre-weaned dairy calves.


docid: wzxlqdov

title: Effect of COVID-19 related lockdown on ophthalmic practice and patient care in India: Results of a survey

text: PURPOSE: In early 2020, the World Health Organization declared the outbreak of the disease COVID-19, caused by a new variant of coronavirus 2019-nCoV as a global pandemic. The government of India ordered a nationwide lockdown for 21 days, limiting movement of people as a preventive measure. This survey was designed and conducted during the lockdown period to assess its effect on ophthalmic practice and patient care in India. METHODS: An online survey was sent across to practicing Indian ophthalmologists across through various social media platforms. All valid responses were tabulated and analyzed. RESULTS: A total of 1260 ophthalmologists responded to the survey. Most of the respondents (775/1260; 61.5%) were in private practice and 14.8% (187/1260) were affiliated to ophthalmic institutes. At the time of taking the survey, 72.5% of the respondents (913/1260) were not seeing any patients due to the lockdown. Of those who were still examining patients, 82.9% (287/347) were only seeing emergency cases, based on their own clinical judgement. The proportion of ophthalmologists in ophthalmic institutes, government and municipal hospitals (126/253;49.8%) who were still seeing patients was significantly higher (P < 0.0001) than those in private practice (174/775;22.4%). Apart from emergencies such as trauma, retinal detachment, and endophthalmitis (81.8%), other surgeries that were still being performed included intravitreal injections (9.1%) and cataract surgeries (5.9%). Approximately, 77.5% (976/1260) of the respondents had begun telephonic/e-mail/video consultations or consultations over social media applications since the lockdown began. In addition, 59.1% (745/1260) felt that ophthalmologists were potentially at a higher risk of contracting COVID-19 compared to other specialties while examining patients. When asked about the resumption of practice upon easing off of the restrictions, 57.8% (728/1260) of the respondents said they were unsure of when to resume elective surgeries; furthermore, 62.8% (791/1260) were unsure about the preferred screening strategy or precautionary approach prior to resuming surgeries and were awaiting guidelines. CONCLUSION: Our survey shows that majority of ophthalmologists in India were not seeing patients during the COVID-19 lockdown, with near-total cessation of elective surgeries. Emergency services were still being attended to by 27.5% of ophthalmologists who responded. A large proportions of ophthalmologists had switched over to telephonic advice or other forms of telemedicine to assist patients. Most of the responding ophthalmologists were unclear about when and how to resume surgeries upon easing off of the COVID-19 related restrictions. Regulatory bodies should take note of this and issue appropriate guidelines regarding the same.


Cannabinoids and the Coronavirus.


title: An insight into the epitope-based peptide vaccine design strategy and studies against COVID-19

text: SARS-CoV-2 is a new member of the coronavirus family and caused the pandemic of coronavirus disease 2019 (COVID-19) in 2020. It is crucial to design and produce an effective vaccine for the prevention of rapid transmission and possible deaths wcaused by the disease. Although intensive work and research are being carried out all over the world to develop a vaccine, an effective and approved formulation that can prevent the infection and limit the outbreak has not been announced yet. Among all types of vaccines, epitope-based peptide vaccines outshine with their low-cost production, easy modification in the structure, and safety. In this review, vaccine studies against COVID-19 have been summarized and detailed information about the epitope-based peptide vaccines against COVID-19 has been provided. We have not only compared the peptide vaccine with other types of vaccines but also presented comprehensive literature information about development steps for an effective and protective formulation to give an insight into on-going peptide vaccine studies against SARS-CoV-2.


title: Nipah Virus Infection Outbreak with Nosocomial and Corpse-to-Human Transmission, Bangladesh

text: Active Nipah virus encephalitis surveillance identified an encephalitis cluster and sporadic cases in Faridpur, Bangladesh, in January 2010. We identified 16 case-patients; 14 of these patients died. For 1 case-patient, the only known exposure was hugging a deceased patient with a probable case, while another case-patient’s exposure involved preparing the same corpse for burial by removing oral secretions and anogenital excreta with a cloth and bare hands. Among 7 persons with confirmed sporadic cases, 6 died, including a physician who had physically examined encephalitis patients without gloves or a mask. Nipah virus–infected patients were more likely than community-based controls to report drinking raw date palm sap and to have had physical contact with an encephalitis patient (29% vs. 4%, matched odds ratio undefined). Efforts to prevent transmission should focus on reducing caregivers’ exposure to infected patients’ bodily secretions during care and traditional burial practices.


title: Whose life to save? Scarce resources allocation in the COVID-19 outbreak

text: After initially emerging in China, the coronavirus (COVID-19) outbreak has advanced rapidly. The World Health Organization (WHO) has recently declared it a pandemic, with Europe becoming its new epicentre. Italy has so far been the most severely hit European country and demand for critical care in the northern region currently exceeds its supply. This raises significant ethical concerns, among which is the allocation of scarce resources. Professionals are considering the prioritisation of patients most likely to survive over those with remote chances, and this news has triggered an intense debate about the right of every individual to access healthcare. The proposed analysis suggests that the national emergency framework in which prioritisation criteria are currently enforced should not lead us to perceive scarce resources allocation as something new. From an ethical perspective, the novelty of the current emergency is not grounded in the devastating effects of scarce resources allocation, which is rife in recent and present clinical practice. Rather, it has to do with the extraordinarily high number of people who find themselves personally affected by the implications of scarce resources allocation and who suddenly realise that the principle of ‘equals should be treated equally’ may no longer be applicable. Along with the need to allocate appropriate additional financial resources to support the healthcare system, and thus to mitigate the scarcity of resources, the analysis insists on the relevance of a medical ethics perspective that does not place the burden of care and choice solely on physicians.


Curcumin as a potential treatment for COVID‐19


title: Structure of the N-terminal dimerization domain of CEACAM7

text: CEACAM7 is a human cellular adhesion protein that is expressed on the surface of colon and rectum epithelial cells and is downregulated in colorectal cancers. It achieves cell adhesion through dimerization of the N-terminal IgV domain. The crystal structure of the N-terminal dimerization domain of CEACAM has been determined at 1.47 Å resolution. The overall fold of CEACAM7 is similar to those of CEACAM1 and CEACAM5; however, there are differences, the most notable of which is an insertion that causes the C′′ strand to buckle, leading to the creation of a hydrogen bond in the dimerization interface. The K (dimerization) for CEACAM7 determined by sedimentation equilibrium is tenfold tighter than that measured for CEACAM5. These findings suggest that the dimerization affinities of CEACAMs are modulated via sequence variation in the dimerization surface.


title: Review: 2-mercaptoethanol alteration of in vitro immune functions of species other than murine

text: Descriptions that organosulfurs could alter biologically relevant cellular functions began some 40 years ago when cell mediated and humoral murine in vitro immune responses were reported to be dramatically enhanced by any of four xenobiotic, sulfhydryl compounds—2-mercaptoethanol (2-ME), dithiothreitol, glutathione, and L-cysteine; the most effective of the four was 2-ME. These findings triggered a plethora of reports defining 2-ME benefits for a multitude of immunological processes, primarily with murine models. This led to investigations on 2-ME alterations of (a) immune functions in other species, (b) activities of other cell-types, and (c) in situ diseases. In addition, the early findings may have been instrumental in identification of the previously undefined anticarcinogenic chemicals in specific foods as organosulfurs. Outside the plant organosulfurs, there are no comprehensive reviews of these areas to help define mechanisms by which organosulfurs function as well as identify potential alternative uses. Therefore, the present review will focus on 2-ME alterations of in vitro immune functions in species other than murine; namely, fish, amphibian, reptile, avian, whales, dolphins, rat, hamster, rabbit, guinea pig, feline, canine, porcine, ovine, bovine, and human. Processes, some unique to a given species, were in general, enhanced and in some cases dependent upon the presence of 2-ME. The largest benefits occurred in media that were serum free, followed by those in autologous serum and then fetal bovine serum supplemented medium. Concentrations of 2-ME were generally in the low μM range, with exceptions of those for salamander (20 mM), turtles (70 mM) and dolphins (7 mM). The few studies designed to assess mechanisms found that changes induced by 2-ME were generally accompanied by alterations of reduced/oxidized glutathione cellular concentrations. The major benefit for most studies, however, was to increase the sensitivity of the culture environment, which permitted a specific process to be more easily dissected.


title: Care of the Geriatric Rabbit

text: The average life span reported in laboratory and lay literature for the domestic rabbit is 5 to 10 years. The author and other veterinarians are now regularly seeing rabbits living to 9 or 10 years, the oldest reported in the author's practice being 14 years. Rabbits are herbivorous prey species with continually growing (elodont) teeth. This feature allows the geriatric rabbit to possess teeth that are essentially “new”, a distinct advantage over geriatric carnivores. Expanded longevity, while generally desirable, necessarily accompanies an increase in geriatric disorders. This article examines the spectrum of disease that can affect the geriatric rabbit as well as crucial factors concerning the clinical management of the animal up to the end of its life. An improved understanding of geriatric disorders in pet rabbits allows early recognition and the opportunity to improve quality of life.


Determination of Length of Time for “Postaerosol Pause” for Patients Under Investigation or Positive for Coronavirus Disease 2019


title: COVID‐19 impact on fruit and vegetable markets

text: Canadian fruit and vegetable markets were significantly impacted by the spread of the novel coronavirus SARS‐CoV‐2 (and COVID‐19 disease), beginning in March 2020. Due to the closure of restaurants, bars, and schools, produce growers and distributors were forced to shift supplies almost entirely from the foodservice to the retail channel. Shippers reported labor and logistical constraints in making the change, but the fresh produce supply chain remained robust. In the long term, we expect lasting changes in consumers’ online food‐purchasing habits, heightened constraints on immigrant labor markets, and tighter concentration in fresh produce distribution and perhaps retailing.


title: Dipeptidyl peptidase-4 (DPP4) inhibition in COVID-19

text: AIMS: SARS–CoV-2 causes severe respiratory syndrome (COVID-19) with high mortality due to a direct cytotoxic viral effect and a severe systemic inflammation. We are herein discussing a possible novel therapeutic tool for COVID-19. METHODS: Virus binds to the cell surface receptor ACE2; indeed, recent evidences suggested that SARS–CoV-2 may be using as co-receptor, when entering the cells, the same one used by MERS–Co-V, namely the DPP4/CD26 receptor. The aforementioned observation underlined that mechanism of cell entry is supposedly similar among different coronavirus, that the co-expression of ACE2 and DPP4/CD26 could identify those cells targeted by different human coronaviruses and that clinical complications may be similar. RESULTS: The DPP4 family/system was implicated in various physiological processes and diseases of the immune system, and DPP4/CD26 is variously expressed on epithelia and endothelia of the systemic vasculature, lung, kidney, small intestine and heart. In particular, DPP4 distribution in the human respiratory tract may facilitate the entrance of the virus into the airway tract itself and could contribute to the development of cytokine storm and immunopathology in causing fatal COVID-19 pneumonia. CONCLUSIONS: The use of DPP4 inhibitors, such as gliptins, in patients with COVID-19 with, or even without, type 2 diabetes, may offer a simple way to reduce the virus entry and replication into the airways and to hamper the sustained cytokine storm and inflammation within the lung in patients diagnosed with COVID-19 infection.


title: Non-antibiotic Possibilities in Prevention and Treatment of Calf Diarrhoea

text: Due to increasing bacterial antibiotic resistance and the consumers’ tendency to choose organic products, cattle farmers are interested in alternative methods of calf diarrhoea treatment. This is a major challenge for veterinarians. Few methods of non-antibiotic treatment that bring satisfactory results have been reported in the related literature so far. In this article, the authors compare different non-antibiotic methods of diarrhoea prevention and treatment in calves. Among the alternatives discussed are herbs, probiotics, prebiotics and synbiotics, lactoferrin, and bacteriophages. It was found that the best results could be achieved through the use of pro-, pre- and synbiotics. However, the authors would like to point out that with the expansion of knowledge about the practical use of broad-scale bacteriophages, they could be the best alternative to antibiotics.


title: A Review of Eight High-Priority, Economically Important Viral Pathogens of Poultry within the Caribbean Region

text: Viral pathogens cause devastating economic losses in poultry industries worldwide. The Caribbean region, which boasts some of the highest rates of poultry consumption in the world, is no exception. This review summarizes evidence for the circulation and spread of eight high-priority, economically important poultry viruses across the Caribbean region. Avian influenza virus (AIV), infectious bronchitis virus (IBV), Newcastle disease virus (NDV), infectious laryngotracheitis virus (ILTV), avian metapneumovirus (aMPV), infectious bursal disease virus (IBDV), fowl adenovirus group 1 (FADV Gp1), and egg drop syndrome virus (EDSV) were selected for review. This review of serological, molecular, and phylogenetic studies across Caribbean countries reveals evidence for sporadic outbreaks of respiratory disease caused by notifiable viral pathogens (AIV, IBV, NDV, and ILTV), as well as outbreaks of diseases caused by immunosuppressive viral pathogens (IBDV and FADV Gp1). This review highlights the need to strengthen current levels of surveillance and reporting for poultry diseases in domestic and wild bird populations across the Caribbean, as well as the need to strengthen the diagnostic capacity and capability of Caribbean national veterinary diagnostic laboratories.


title: Extrapulmonary Gastrointestinal Presentation of Coronavirus (COVID-19): A Case Report and Review of Literature

text: Coronavirus disease 2019 (COVID-19) is currently the causative agent for a global health emergency and is predominantly associated with respiratory symptoms. In this case, a patient presented to the emergency department with gastrointestinal symptomatology without associated respiratory findings and was subsequently diagnosed with COVID-19 based on incidental findings from an abdominal computed tomography (CT) study. Given the patient’s lack of respiratory symptoms, diagnosis and treatment were ultimately delayed. During this global health crisis, an improved understanding of the various presentations of COVID-19 is paramount in an effort to initiate immediate treatment and prevent further transmission.


title: Dying and caring on the edge: Taiwan's surviving nurses' reflections on taking care of patients with severe acute respiratory syndrome

text: Abstract In 2003, Taiwan's nurses were terrified by severe acute respiratory syndrome (SARS), and four of them sacrificed their life in the course of their work with SARS patients. This study attempted to identify the stage-specific difficulties encountered by Taiwan's surviving frontline nurses during the anti-SARS process. A two-step within-method qualitative triangulation research design was used to obtain the in-depth and confidential thoughts of 200 participants during the precaring, tangible caring, and postcaring stages. Six major types of stage-specific difficulties with and threats to the quality of care of SARS patients were identified according to each specific stage of the caring process. Four themes were further explored; these are discussed to provide a background context in obtaining better understanding of the multifaceted needs of nurses during this crisis. Consequently, a conceptual framework was developed to depict this complex phenomenon.


title: The Natural Viral Load Profile of Patients With Pandemic 2009 Influenza A(H1N1) and the Effect of Oseltamivir Treatment

text: Background The natural history of viral shedding from the upper respiratory tract of the new pandemic 2009 influenza A(H1N1) and the effect of oseltamivir treatment were uncertain. Methods A retrospective cohort study involving 145 consecutive patients with specimens positive by reverse transcriptase-polymerase chain reaction for the matrix and new H1 genes was conducted. Results The nontreated and oseltamivir-treated patients were comparable in their viral load at presentation, demography, and the presenting symptoms. No correlation was observed between viral load with age and number of symptoms. Viral load of nasopharyngeal aspirate (NPA) was significantly lower in treated than in nontreated patients at day 5 after symptom onset. When oseltamivir was initiated ≤ 2 days after symptom onset, a greater rate of viral load reduction in NPA of treated patients than that of nontreated patients was observed (−0.638 [95% CI, −0.809 to −0.466] vs −0.409 [95% CI, −0.663 to −0.185] log10 copies/mL/d post-symptom onset), and the viral load was undetectable at day 6 after oseltamivir initiation, which was 1 day earlier than that of those whose treatment was initiated > 2 days of symptom onset. The viral load was inversely correlated with concomitant absolute lymphocyte count in nontreated patients (Pearson correlation coefficient [r] = −0.687, P = .001) and treated patients (Pearson r = −0.365, P < .001). Resolution of fever was 1.4 days later in nontreated than treated patients (P = .012) Conclusions The natural viral load profile was described. Oral oseltamivir suppresses viral load more effectively when given early in mild cases of pandemic 2009 influenza A(H1N1) infections.


docid: ezgrfdhb

title: A Review on Emerging and Reemerging of Infectious Diseases in Jordan: The Aftermath of the Syrian Crises

text: The review aims to examine the emergence and reemergence of infectious diseases in Jordan, in parallel with the Syrian refugee crisis. Qualitative approach has been adopted for systematically examining the outcomes of the Syrian crisis, which resulted in emerging and reemerging infectious diseases. It has adhered that infectious diseases, including measles, tuberculosis, and cutaneous leishmaniasis, have hazardous effects on Syrian refugees along with the local population in Jordan. The threat of major infectious diseases is higher and alarming in Jordan. National health policies should be implemented to adhere the influence of infectious diseases as well as to reduce the extent of infectious diseases in Jordan. In the 21st century, Syrian conflict can be deliberated as one of the biggest humanitarian disasters. In this multifaceted emergency with devastating requirements and limitations, it has been found essential for dominant medical healthcare providers to develop medical strategies that are based on comprehensive understanding of the concerned context and the main medical requirements and susceptible groups.


title: Transition to Virtual Learning During the Coronavirus Disease–2019 Crisis in Iran: Opportunity Or Challenge?

text: COVID-19 is a respiratory disease that can spread from one person to person. This virus is a novel coronavirus that was first identified during an investigation into an outbreak in Wuhan, China. Iran’s novel coronavirus cases reached 17,361 on 17 March, while death toll reached approximately 1,135. Its first death was officially announced on 20 February 2020 in Qom. The 2019 coronavirus pandemic has affected educational systems around the world, Also in Iran, and led to the closure of face to face courses in schools and universities. Therefore, virtual education can be seen as a turning point in education of these days in Iran.


title: Flavonoids: promising natural compounds against viral infections

text: Flavonoids are widely distributed as secondary metabolites produced by plants and play important roles in plant physiology, having a variety of potential biological benefits such as antioxidant, anti-inflammatory, anticancer, antibacterial, antifungal and antiviral activity. Different flavonoids have been investigated for their potential antiviral activities and several of them exhibited significant antiviral properties in in vitro and even in vivo studies. This review summarizes the evidence for antiviral activity of different flavonoids, highlighting, where investigated, the cellular and molecular mechanisms of action on viruses. We also present future perspectives on therapeutic applications of flavonoids against viral infections.


title: Genus Psoralea: A review of the traditional and modern uses, phytochemistry and pharmacology

text: Abstract Ethnopharmacological relevance The genus Psoralea (Fabaceae) harbours 105 accepted species that are extensively used by local peoples and medicinal practitioners of China, India, and other countries for treatment of tooth decay, psoriasis, leucoderma, leprosy, kidney problems, tuberculosis, indigestion, constipation and impotence. Presently, pharmacological research reports are available on only few species namely Bituminaria bituminosa (Syn: P. bituminosa), P. canescens, P. corylifolia, P. esculenta, P. plicata and P. glandulosa which are valued for their chemical constituents and traditional uses. Aim of the review This review article provides explicit information on traditional uses, phytochemistry, and pharmacological activities of selected Psoralea species. The possible trends and perspectives for future research on these plants are also discussed. Materials and methods An extensive and systematic review of the extant literature was carried out, and the data under various sections were identified using a computerized bibliographic search via the PubMed, Web of Science and Google Scholar, CAB Abstracts, MEDLINE, EMBASE, INMEDPLAN, NATTS as well as several websites. Key findings A total of 291 bioactive compounds from 06 species of genus Psoralea have been isolated and characterized. However, P. bituminosa alone possess nearly 150 compounds. These bioactive compounds belong to different chemical classes, including flavonoids, coumarins, furanocoumarins, chalcones, quinines, terpenoids and some others due to which these species exhibit significant anti-oxidant, anti-bacterial, anti-fungal, anti-viral, anti-helmintic, anti-diabetic, diuretic, hepatoprotective, anti-cancer and anti-tumor activities. P. corylifolia L. (Babchi), a Chinese traditional medicinal plant has been used in traditional medicine for many decades for its healing properties against numerous skin diseases such as leprosy, psoriasis and leucoderma. Conclusions The in vitro studies and in vivo models have provided a simple bio-scientific justification for various ethnopharmacological uses of Psoralea species. From the toxicological perspective, the root, leaf, and seed extracts and their preparations have been proven to be safe when consumed in the recommended doses. But, meticulous studies on the pharmaceutical standardization, mode of action of the active constituents, and sustainable conservation of Psoralea species are needed, to meet the growing demands of the pharmaceutical industries, and to fully exploit their preventive and therapeutic potentials.


title: No evidence for European bats serving as reservoir for Borna disease virus 1 or other known mammalian orthobornaviruses

text: BACKGROUND: The majority of emerging infectious diseases are zoonotic in nature and originate from wildlife reservoirs. Borna disease, caused by Borna disease virus 1 (BoDV-1), is an infectious disease affecting mammals, but recently it has also been shown to cause fatal encephalitis in humans. The endemic character of Borna disease points towards a nature-bound reservoir, with only one shrew species identified as reservoir host to date. Bats have been identified as reservoirs of a variety of zoonotic infectious agents. Endogenous borna-like elements in the genome of certain bat species additionally point towards co-evolution of bats with bornaviruses and therefore raise the question whether bats could serve as a potential reservoir of orthobornaviruses. METHODS: Frozen brain samples (n = 257) of bats of seven different genera from Germany were investigated by orthobornaviral RT-PCR. Additionally, tissue slides of formalin-fixed paraffin-embedded material of a subset of these bats (n = 140) were investigated for orthobornaviral phosphoprotein by immunohistochemistry. RESULTS: The brain samples were tested by RT-PCR without any evidence of orthobornavirus specific amplicons. Immunohistochemistry revealed a faint immunoreaction in 3/140 bats but with an untypical staining pattern for viral antigen. CONCLUSIONS: RT-PCR-screening showed no evidence for orthobornaviral RNA in the investigated bats. However, immunohistochemistry results should be investigated further to elucidate whether the reaction might be associated with expressed endogenous bornaviral elements or other so far unknown bornaviruses.


title: Is SARS-CoV-2 Also an Enteric Pathogen with Potential Fecal-Oral Transmission: A COVID-19 Virological and Clinical Review

text: Abstract In as short as 3 months, COVID-19 has spread and ravaged the world in an unprecedented speed in modern history rivaling the 1918 flu pandemic. SARS-CoV-2, the culprit virus, is highly contagious and stable in the environment and predominantly transmits among humans via the respiratory route. Accumulating evidence suggest that this virus, like many of its related viruses, may also be an enteric virus that can spread via the fecal-oral route. Such a hypothesis would also contribute to the rapidity and proliferation of this pandemic. Here we briefly summarize what is known about this family of viruses and literature basis of the hypothesis that SARS-CoV-2 is capable of infecting the gastrointestinal tract and shedding in the environment for potential human-to-human transmission.


title: Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020

text: We describe clinical characteristics, treatments and outcomes of 44 Caucasian patients with coronavirus disease (COVID-19) at a single hospital in Pavia, Italy, from 21–28 February 2020, at the beginning of the outbreak in Europe. Seventeen patients developed severe disease, two died. After a median of 6 days, 14 patients were discharged from hospital. Predictors of lower odds of discharge were age > 65 years, antiviral treatment and for severe disease, lactate dehydrogenase > 300 mg/dL.


title: Epidemiological study of zoonoses derived from humans in captive chimpanzees

text: Emerging infectious diseases (EIDs) in wildlife are major threats both to human health and to biodiversity conservation. An estimated 71.8 % of zoonotic EID events are caused by pathogens in wildlife and the incidence of such diseases is increasing significantly in humans. In addition, human diseases are starting to infect wildlife, especially non-human primates. The chimpanzee is an endangered species that is threatened by human activity such as deforestation, poaching, and human disease transmission. Recently, several respiratory disease outbreaks that are suspected of having been transmitted by humans have been reported in wild chimpanzees. Therefore, we need to study zoonotic pathogens that can threaten captive chimpanzees in primate research institutes. Serological surveillance is one of several methods used to reveal infection history. We examined serum from 14 captive chimpanzees in Japanese primate research institutes for antibodies against 62 human pathogens and 1 chimpanzee-borne infectious disease. Antibodies tested positive against 29 pathogens at high or low prevalence in the chimpanzees. These results suggest that the proportions of human-borne infections may reflect the chimpanzee’s history, management system in the institute, or regional epidemics. Furthermore, captive chimpanzees are highly susceptible to human pathogens, and their induced antibodies reveal not only their history of infection, but also the possibility of protection against human pathogens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10329-012-0320-8) contains supplementary material, which is available to authorized users.


Cardiovascular emergencies in the COVID-19 pandemic


title: Mutualistic viruses and the heteronomy of life

text: Abstract Though viruses have generally been characterized by their pathogenic and more generally harmful effects, many examples of mutualistic viruses exist. Here I explain how the idea of mutualistic viruses has been defended in recent virology, and I explore four important conceptual and practical consequences of this idea. I ask to what extent this research modifies the way scientists might search for new viruses, our notion of how the host immune system interacts with microbes, the development of new therapeutic approaches, and, finally, the role played by the criterion of autonomy in our understanding of living things. Overall, I suggest that the recognition of mutualistic viruses plays a major role in a wider ongoing revision of our conception of viruses.


title: Estimating the COVID-19 cash crunch: Global evidence and policy

text: Abstract In this paper, we investigate how the COVID-19 health crisis could affect the liquidity of listed firms across 26 countries. We stress-test three liquidity ratios for each firm with full and partial operating flexibility in two simulated distress scenarios corresponding to drops in sales of 50% and 75%, respectively. In the most adverse scenario, the average firm with partial operating flexibility would exhaust its cash holdings in about two years. At that point, its current liabilities would increase, on average, by eight times, suggesting that the average firm would have to resort to the debt market to prevent a liquidity crunch. Moreover, about 1/10th of all sample firms would become illiquid within six months. Finally, we study two different fiscal policies, tax deferrals and bridge loans, that governments could implement to mitigate the liquidity risk. Our analysis suggests bridge loans are more cost-effective to prevent a massive cash crunch.


title: Medical masks vs N95 respirators for preventing COVID‐19 in healthcare workers: A systematic review and meta‐analysis of randomized trials

text: BACKGROUND: Respiratory protective devices are critical in protecting against infection in healthcare workers at high risk of novel 2019 coronavirus disease (COVID‐19); however, recommendations are conflicting and epidemiological data on their relative effectiveness against COVID‐19 are limited. PURPOSE: To compare medical masks to N95 respirators in preventing laboratory‐confirmed viral infection and respiratory illness including coronavirus specifically in healthcare workers. DATA SOURCES: MEDLINE, Embase, and CENTRAL from January 1, 2014, to March 9, 2020. Update of published search conducted from January 1, 1990, to December 9, 2014. STUDY SELECTION: Randomized controlled trials (RCTs) comparing the protective effect of medical masks to N95 respirators in healthcare workers. DATA EXTRACTION: Reviewer pair independently screened, extracted data, and assessed risk of bias and the certainty of the evidence. DATA SYNTHESIS: Four RCTs were meta‐analyzed adjusting for clustering. Compared with N95 respirators; the use of medical masks did not increase laboratory‐confirmed viral (including coronaviruses) respiratory infection (OR 1.06; 95% CI 0.90‐1.25; I (2) = 0%; low certainty in the evidence) or clinical respiratory illness (OR 1.49; 95% CI: 0.98‐2.28; I (2) = 78%; very low certainty in the evidence). Only one trial evaluated coronaviruses separately and found no difference between the two groups (P = .49). LIMITATIONS: Indirectness and imprecision of available evidence. CONCLUSIONS: Low certainty evidence suggests that medical masks and N95 respirators offer similar protection against viral respiratory infection including coronavirus in healthcare workers during non–aerosol‐generating care. Preservation of N95 respirators for high‐risk, aerosol‐generating procedures in this pandemic should be considered when in short supply.


title: Formatted for Journal of Clinical Virology

text: BACKGROUND: Human rhinovirus (HRV) infections are highly prevalent, genetically diverse, and associated with both mild upper respiratory tract and more severe lower tract illnesses (LRTI). OBJECTIVE: To characterize the molecular epidemiology of HRV infections in young children seeking acute medical care. STUDY DESIGN: Nasal swabs collected from symptomatic children <3 years of age receiving care in the Emergency and Urgent Care Departments at Seattle Children's Hospital were analyzed by a rapid polymerase chain reaction (PCR) system (FilmArray®) for multiple viruses including HRV/enterovirus. HRV-positive results were confirmed by laboratory-developed real-time reverse transcription PCR (LD-PCR). Clinical data were collected by chart review. A subset of samples was selected for sequencing using the 5’ noncoding region. Associations between LRTI and HRV species and genotypes were estimated using logistic regression analysis. RESULTS: Of 595 samples with HRV/enterovirus detected by FilmArray, 474 (80%) were confirmed as HRV by LD-PCR. 211 (96%) of 218 selected samples were sequenced; HRV species A, B, and C were identified in 133 (63%), 6 (3%), and 72 (34%), respectively. LRTI was more common in HRVC than HRV-A illness episodes (adjusted OR [95% CI] 2.35[1.03-5.35). Specific HRV-A and HRV-C genotypes detected in multiple patients were associated with a greater proportion of LRTI episodes. In 18 patients with >1 HRV-positive illness episodes, a distinct genotype was detected in each. CONCLUSION: Diverse HRV genotypes circulated among symptomatic children during the study period. We found an association between HRV-C infections and LRTI in this patient population and evidence of association between specific HRV genotypes and LRTI.


title: Infecção na modulaçâo da asma 1 1 Trabalho apresentado no XXIII Congresso de Pneumologia da SPP – Guarda, Novembro 2007 / Paper presented at the XXIII Congresso de Pneumologia da SPP / PSP Pulmonology Congress, Guarda, November 2007

text: Abstract This paper reviews the impact of infections on the onset and clinical course of bronchial asthma. A just emphasis is given to the role viral infections, particularly rhinovirus infections, play in exacerbations, and that played by respiratory syncytial virus, suspected of triggering the asthmatic syndrome. The mechanisms of the immune response to virus attacks are explained, highlighting the asthmatic and allergic patient’s weakened response, particularly in the perinatal period. Further stressed is a potentiating effect of viral aggression on the allergic response. The hygiene hypothesis and its lack of scientific consistency is detailed, at least as far as the role it seeks to confer on an unproven antagonism of the Th1 and Th2 lymphocyte responses. The current importance of research not into bacteria, but into bacterial products, including endotoxins, on the modulation of asthma and allergy is noted. Studies which, along these lines, show an environmental impact on genetic secretion in the phenotype are underlined. Also discussed in passing are several mechanisms which go towards explaining neutrophilic asthma – for many a contradiction, given eosinophilia’s stranglehold on asthmatic inflammation. Rev Port Pneumol 2008; XIV (5): 647-675


title: A Decade On: Systematic Review of ClinicalTrials.gov Infectious Disease Trials, 2007–2017

text: BACKGROUND: Registration of interventional trials of Food and Drug Administration–regulated drug and biological products and devices became a legal requirement in 2007; the vast majority of these trials are registered in ClinicalTrials.gov. An analysis of ClinicalTrials.gov offers an opportunity to define the clinical research landscape; here we analyze 10 years of infectious disease (ID) clinical trial research. METHODS: Beginning with 166 415 interventional trials registered in ClinicalTrials.gov from 2007–2017, ID trials were selected by study conditions and interventions. Relevance to ID was confirmed through manual review, resulting in 13 707 ID trials and 152 708 non-ID trials. RESULTS: ID-related trials represented 6.9%–9.9% of all trials with no significant trend over time. ID trials tended to be more focused on treatment and prevention, with a focus on testing drugs, biologics, and vaccines. ID trials tended to be large, randomized, and nonblinded with a greater degree of international enrollment. Industry was the primary funding source for 45.2% of ID trials. Compared with the global burden of disease, human immunodeficiency virus/AIDS and hepatitis C trials were overrepresented, and lower respiratory tract infection trials were underrepresented. Hepatitis C trials fluctuated, keeping with a wave of new drug development. Influenza vaccine trials peaked during the 2009 H1N1 swine influenza outbreak. CONCLUSIONS: This study presents the most comprehensive characterization of ID clinical trials over the past decade. These results help define how clinical research aligns with clinical need. Temporal trends reflect changes in disease epidemiology and the impact of scientific discovery and market forces. Periodic review of ID clinical trials can help identify gaps and serve as a mechanism to realign resources.


docid: warwruiu

title: Antiviral effects of probiotic metabolites on COVID-19

text: SARS coronavirus (COVID-19) is a real health challenge of the 21st century for scientists, health workers, politicians, and all humans that has severe cause epidemic worldwide. The virus exerts its pathogenic activity through by mechanism and gains the entry via spike proteins (S) and Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins on host cells. The present work is an effort for a computational target to block the residual binding protein (RBP) on spike proteins (S), Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins by probiotics namely Plantaricin BN, Plantaricin JLA-9, Plantaricin W, Plantaricin D along with RNA-dependent RNA polymerase (RdRp). Docking studies were designed in order to obtain the binding energies for Plantaricin metabolites. The binding energies for Plantaricin W were −14.64, −11.1 and −12.68 for polymerase, RBD and ACE2 respectively comparatively very high with other compounds. Plantaricin W, D, and JLA-9 were able to block the residues (THR556, ALA558) surrounding the deep grove catalytic site (VAL557) of RdRp making them more therapeutically active for COVID-19. Molecular dynamics studies further strengthen stability of the complexes of plantaricin w and SARS-CoV-2 RdRp enzyme, RBD of spike protein, and human ACE2 receptor. The present study present multi-way options either by blocking RBD on S proteins or interaction of S protein with ACE2 receptor proteins or inhibiting RdRp to counter any effect of COVID-19 by Plantaricin molecules paving a way that can be useful in the treatment of COVID-19 until some better option will be available. Communicated by Ramaswamy H. Sarma


Counterfeit Filtering Facepiece Respirators are posing an additional Risk to Healthcare Workers during COVID-19 Pandemic


• Novel case report highlighting association of COVID-19 precipitating symptoms of CADASIL; • Multiple internal border zone infarcts in a patient with COVID-19 and CADASIL; • Proposed mechanism is endothelial injury with microvascular thrombosis and cerebral dysautoregulation; • We advise to consider patients with CADASIL a vulnerable group during the pandemic.


The COVID‐19 Pandemic: Experiences of a Geriatrician‐Hospitalist Caring for Older Adults


title: Computational Forecasting Methodology for Acute Respiratory Infectious Disease Dynamics

text: The study of infectious disease behavior has been a scientific concern for many years as early identification of outbreaks provides great advantages including timely implementation of public health measures to limit the spread of an epidemic. We propose a methodology that merges the predictions of (i) a computational model with machine learning, (ii) a projection model, and (iii) a proposed smoothed endemic channel calculation. The predictions are made on weekly acute respiratory infection (ARI) data obtained from epidemiological reports in Mexico, along with the usage of key terms in the Google search engine. The results obtained with this methodology were compared with state-of-the-art techniques resulting in reduced root mean squared percentage error (RMPSE) and maximum absolute percent error (MAPE) metrics, achieving a MAPE of 21.7%. This methodology could be extended to detect and raise alerts on possible outbreaks on ARI as well as for other seasonal infectious diseases.


title: AT2 receptors: Functional relevance in cardiovascular disease

text: Abstract The renin angiotensin system (RAS) is intricately involved in normal cardiovascular homeostasis. Excessive stimulation by the octapeptide angiotensin II contributes to a range of cardiovascular pathologies and diseases via angiotensin type 1 receptor (AT1R) activation. On the other hand, tElsevier Inc.he angiotensin type 2 receptor (AT2R) is thought to counter-regulate AT1R function. In this review, we describe the enhanced expression and function of AT2R in various cardiovascular disease settings. In addition, we illustrate that the RAS consists of a family of angiotensin peptides that exert cardiovascular effects that are often distinct from those of Ang II. During cardiovascular disease, there is likely to be an increased functional importance of AT2R, stimulated by Ang II, or even shorter angiotensin peptide fragments, to limit AT1R-mediated overactivity and cardiovascular pathologies.


title: COVID‐19 epidemic: Disease characteristics in children

text: In mid‐December 2019, a disease caused by infection with severe acute respiratory syndrome coronavirus‐2, which began in Wuhan, China, has spread throughout the country and many countries around the world. The number of children with coronavirus disease‐2019 (COVID‐19) has also increased significantly. Although information regarding the epidemiology of COVID‐19 in children has accumulated, relevant comprehensive reports are lacking. The present article reviews the epidemiological characteristics of COVID‐19 in children.


title: Biflavonoids from Torreya nucifera displaying SARS-CoV 3CLpro inhibition

text: Abstract As part of our search for botanical sources of SARS-CoV 3CLpro inhibitors, we selected Torreya nucifera, which is traditionally used as a medicinal plant in Asia. The ethanol extract of T. nucifera leaves exhibited good SARS-CoV 3CLpro inhibitory activity (62% at 100μg/mL). Following bioactivity-guided fractionation, eight diterpenoids (1–8) and four biflavonoids (9–12) were isolated and evaluated for SARS-CoV 3CLpro inhibition using fluorescence resonance energy transfer analysis. Of these compounds, the biflavone amentoflavone (9) (IC50 =8.3μM) showed most potent 3CLpro inhibitory effect. Three additional authentic flavones (apigenin, luteolin and quercetin) were tested to establish the basic structure–activity relationship of biflavones. Apigenin, luteolin, and quercetin inhibited 3CLpro activity with IC50 values of 280.8, 20.2, and 23.8μM, respectively. Values of binding energy obtained in a molecular docking study supported the results of enzymatic assays. More potent activity appeared to be associated with the presence of an apigenin moiety at position C-3′ of flavones, as biflavone had an effect on 3CLpro inhibitory activity.


title: COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome?

text: Abstract The severe form of COVID-19 share several clinical and laboratory features with four entities gathered under the term “hyperferritinemic syndrome” and including macrophage activation syndrome (MAS), adult-onset Still's disease (AOSD), catastrophic anti-phospholipid syndrome (CAPS) and septic shock. COVID-19 systemic inflammatory reaction and “hyperferritinemic syndromes” are all characterized by high serum ferritin and a life-threatening hyper-inflammation sustained by a cytokines storm which eventually leads to multi-organ failure. In this review, we analyze the possible epidemiological and molecular mechanisms responsible for hyper-inflammation in patients with severe COVID-19 and we underline the similarities between this condition and “hyperferritinemic syndromes” which would allow considering this entity as the fifth member of the spectrum of inflammatory conditions.


title: Early report on published outcomes in kidney transplant recipients compared to non-transplant patients infected with COVID-19

text: Abstract Background Kidney transplant recipients (KTR) present unique characteristics including disease vintage, immunosuppression, and single functioning kidneys. We conducted preliminary analyses to assess the impact of COVID-19 on outcomes in KTR compared to non-transplant patients. Methods We evaluated published information in peer-reviewed journals between 01/01/20 and 04/24/2020 with available data on AKI, renal replacement therapy (RRT), intensive care unit (ICU) stay, and death, and compared clinical outcomes in KTR versus non-transplant recipients with COVID-19. Results A total of 19 published articles were identified, including a total of 88 KTR and 5,342 non-transplant patients. The sample size varied between 2 and 2,634. Mean age was 58.6 years vs. 58.9 years in KTR vs. non-transplant. Patient-level incidence of AKI (27.5% vs. 13.3%, p<0.001), RRT (15.4% vs. 3.3%, p<0.001), ICU stay (34.1% vs. 15.1%, p<0.001), and death (22.7% vs 16.2%, p=0.10), was higher in KTR, representing relative risks of 2.06 (1.44, 2.96), 4.72 (2.62, 8.51), 2.25 (1.67, 3.03), and 1.41 (0.95, 2.08), respectively. Conclusion Early results suggest that the KTR are at significantly greater risk of AKI, RRT, and ICU stay from COVID-19 infection compared to the general population. The risk of death may not be significantly different.


title: Parallels among positive-strand RNA viruses, reverse-transcribing viruses and double-stranded RNA viruses

text: Viruses are divided into seven classes on the basis of differing strategies for storing and replicating their genomes through RNA and/or DNA intermediates. Despite major differences among these classes, recent results reveal that the non-virion, intracellular RNA-replication complexes of some positive-strand RNA viruses share parallels with the structure, assembly and function of the replicative cores of extracellular virions of reverse-transcribing viruses and double-stranded RNA viruses. Therefore, at least four of seven principal virus classes share several underlying features in genome replication and might have emerged from common ancestors. This has implications for virus function, evolution and control.


title: Murine Coronavirus Infection Activates the Aryl Hydrocarbon Receptor in an Indoleamine 2,3-Dioxygenase-Independent Manner, Contributing to Cytokine Modulation and Proviral TCDD-Inducible-PARP Expression

text: The aryl hydrocarbon receptor (AhR) is a cytoplasmic receptor/transcription factor that modulates several cellular and immunological processes following activation by pathogen-associated stimuli, though its role during virus infection is largely unknown. Here, we show that AhR is activated in cells infected with mouse hepatitis virus (MHV), a coronavirus (CoV), and contributes to the upregulation of downstream effector TCDD-inducible poly(ADP-ribose) polymerase (TiPARP) during infection. Knockdown of TiPARP reduced viral replication and increased interferon expression, suggesting that TiPARP functions in a proviral manner during MHV infection. We also show that MHV replication induced the expression of other genes known to be downstream of AhR in macrophages and dendritic cells and in livers of infected mice. Further, we found that chemically inhibiting or activating AhR reciprocally modulated the expression levels of cytokines induced by infection, specifically, interleukin 1β (IL-1β), IL-10, and tumor necrosis factor alpha (TNF-α), consistent with a role for AhR activation in the host response to MHV infection. Furthermore, while indoleamine 2,3-dioxygenase (IDO1) drives AhR activation in other settings, MHV infection induced equal expression of downstream genes in wild-type (WT) and IDO1(−/−) macrophages, suggesting an alternative pathway of AhR activation. In summary, we show that coronaviruses elicit AhR activation by an IDO1-independent pathway, contributing to upregulation of downstream effectors, including the proviral factor TiPARP, and to modulation of cytokine gene expression, and we identify a previously unappreciated role for AhR signaling in CoV pathogenesis. IMPORTANCE Coronaviruses are a family of positive-sense RNA viruses with human and agricultural significance. Characterizing the mechanisms by which coronavirus infection dictates pathogenesis or counters the host immune response would provide targets for the development of therapeutics. Here, we show that the aryl hydrocarbon receptor (AhR) is activated in cells infected with a prototypic coronavirus, mouse hepatitis virus (MHV), resulting in the expression of several effector genes. AhR is important for modulation of the host immune response to MHV and plays a role in the expression of TiPARP, which we show is required for maximal viral replication. Taken together, our findings highlight a previously unidentified role for AhR in regulating coronavirus replication and the immune response to the virus.


title: The neutrophil in vascular inflammation

text: Here we focus on how neutrophils have a key regulatory role in vascular inflammation. Recent studies using advanced imaging techniques have yielded new insights into the mechanisms by which neutrophils contribute to defense against bacterial infections and also against sterile injury. In these settings, neutrophils are recruited by various mechanisms depending on the situation. We also describe how these processes may be disrupted in systemic infections, with a particular emphasis on mouse models of sepsis. Neutrophils are often immobilized in the lungs and liver during systemic infections, and this immobilization may be a mechanism through which bacteria can evade the innate immune response or allow neutrophils to form neutrophil extracellular traps that trap and kill bacteria in blood. The platelet is also an important player in sepsis, and we describe how it collaborates with neutrophils in the formation of neutrophil extracellular traps. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm.2514) contains supplementary material, which is available to authorized users.


title: Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus

text: The lack of a licensed vaccine for respiratory syncytial virus (RSV) can be partly attributed to regulatory hurdles resulting from vaccine enhanced respiratory disease (ERD) subsequent to natural RSV infection that was observed in clinical trials of formalin-inactivated RSV (FI-RSV) in antigen-naïve infants. To develop an effective vaccine that does not enhance RSV illness, it is important to understand how formalin and heat inactivation affected the antigenicity and immunogenicity of FI-RSV compared to native virus. Informed by atomic structures of RSV fusion (F) glycoprotein in prefusion (pre-F) and postfusion (post-F) conformations, we demonstrate that FI-RSV predominately presents post-F on the virion surface, whereas infectious RSV presents both pre-F and post-F conformations. This significant antigenic distinction has not been previously appreciated. Thus, a stabilized pre-F antigen is more representative of live RSV than F in its post-F conformation, as displayed on the surface of FI-RSV. This finding has major implications for discriminating current pre-F-based immunogens from FI-RSV used in historical vaccine trials.


title: Effective Use of Virtual Gamification During COVID-19 to Deliver the OB-GYN Core Curriculum in an Emergency Medicine Resident Conference

text: Introduction Coronavirus disease 2019 (COVID-19) has challenged medical educators on continuing to provide quality educational content in a virtual setting. The objective of this module was to create a gamified review of core obstetric and gynecology (OB-GYN) topics that residents would find educational and informative. Methods The game created was modeled after the TV show “So You Think You Can Dance?”, with a warm-up and several rounds of rapid-fire OB-GYN questions and cases, eliminating teams to a final face-off. The residents were given a post-session survey to determine their attitudes and learning towards this virtual conference approach. Results Based on the post-session survey, the majority of the residents found this activity to be educational, entertaining, engaging, and better than the traditional lecture format. Conclusion This initial attempt at migrating gamification, a core component of our live conferences, into the new virtual arena, was well-received by learners as effective, educational, and engaging. This style of gamification can be incorporated into residency programs at other institutions currently limited to virtual platforms to boost resident education and engagement.


title: A generic approach to evaluate how B-cell epitopes are surface-exposed on protein structures

text: Abstract Methods that predict antibody epitopes could help to promote the development of diagnostic tools, vaccines or immunotherapies by affecting the epitope binding of antibodies during an immunological response to antigens. It is generally assumed that there is a direct relationship between antibody accessibility to antigens and accessible surface of proteins. Based on this assumption, prediction systems often includes solvent accessibility values calculated from the primary sequence of proteins or from their three dimensional structures as a predictive criterion. However, the current prediction systems seem weakly efficient in view of benchmark tests. We were interested in evaluating how amino acids that have been experimentally identified as epitopic elements could differ from the rest of the antigenic molecule at the level of surface exposure, hence we assessed the average accessibility of epitopes. The approach used here utilises published epitopes deduced from numerous identification techniques, including sequence scanning and structure visualisation after crystallography, and it involves many types of antigens from toxins to allergens. Our results show that epitopic residues are not distributed among any specific Relative Surface Accessibility and Protrusion Index values and that, in some cases, epitopes cover the entire antigenic sequence. These results led to the conclusion that the classification of known epitopes with respect to the experimental conditions used to identify them should be introduced before attempting to characterise epitopic areas in a generic way.


Médicaments rhumatologiques pour le traitement de l’infection par le COVID-19


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title: What orthopedic surgeons need to know about Covid-19 pandemic()

text: The ongoing outbreak of COVID-19, also known as SARS-CoV-2 and coronavirus disease 2019, is considered a major public concern that propagates steadily by the increased number of the infected cases and the mortality rate. In this article, we provide a brief review for Orthopedic surgeons as regard COVID-19 virus microbiology, epidemiology, clinical picture, and diagnosis. Moreover, what measures should be taken amid this pandemic to assess its control, maintain the urgent duties, and protect health care workers (HCW) are also discussed.


BioLogic THERAPY IN COVID-19


title: Barriers to patient, provider, and caregiver adoption and use of electronic personal health records in chronic care: a systematic review

text: BACKGROUND: Electronic personal health records (ePHRs) are defined as electronic applications through which individuals can access, manage, and share health information in a private, secure, and confidential environment. Existing evidence shows their benefits in improving outcomes, especially for chronic disease patients. However, their use has not been as widespread as expected partly due to barriers faced in their adoption and use. We aimed to identify the types of barriers to a patient, provider, and caregiver adoption/use of ePHRs and to analyze their extent in chronic disease care. METHODS: A systematic search in Medline, PubMed, Science Direct, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Central Register of Controlled Trials, and the Institute of Electrical and Electronics Engineers (IEEE) database was performed to find original studies assessing barriers to ePHR adoption/use in chronic care until the end of 2018. Two researchers independently screened and extracted data. We used the PHR adoption model and the Unified Theory of Acceptance and Use of Technology to analyze the results. The Mixed Methods Appraisal Tool (MMAT) version 2018 was used to assess the quality of evidence in the included studies. RESULTS: Sixty publications met our inclusion criteria. Issues found hindering ePHR adoption/use in chronic disease care were associated with demographic factors (e.g., patient age and gender) along with key variables related to health status, computer literacy, preferences for direct communication, and patient’s strategy for coping with a chronic condition; as well as factors related to medical practice/environment (e.g., providers’ lack of interest or resistance to adopting ePHRs due to workload, lack of reimbursement, and lack of user training); technological (e.g., concerns over privacy and security, interoperability with electronic health record systems, and lack of customized features for chronic conditions); and chronic disease characteristics (e.g., multiplicities of co-morbid conditions, settings, and providers involved in chronic care). CONCLUSIONS: ePHRs can be meaningfully used in chronic disease care if they are implemented as a component of comprehensive care models specifically developed for this care. Our results provide insight into hurdles and barriers mitigating ePHR adoption/use in chronic disease care. A deeper understating of the interplay between these barriers will provide opportunities that can lead to an enhanced ePHR adoption/use.


Public health preparedness and response in the USA since 9/11: a national health security imperative


title: Diagnostic performance of immunochromatography assay for rapid detection of IgM and IgG in coronavirus disease 2019

text: Serologic assays have been developed to detect infection with coronavirus disease 2019 (COVID‐19). This study was conducted to evaluate the diagnostic performance of an immunochromatography‐based assay of human serum for COVID‐19. The present study enrolled 149 subjects who had been tested by real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) for COVID‐19 and were classified into two groups: 70 who were positive for COVID‐19 and 79 who were negative for COVID‐19 based on RT‐PCR. An immunochromatography‐based COVID‐19 immunoglobulin G (IgG)/immunoglobulin M (IgM) rapid test on the sera of the study population was applied to measure the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) curve compared to RT‐PCR, with a 95% confidence interval (CI). IgM or IgG antibodies were detected in 65 subjects (92.9%) classified as positive for COVID‐19 and in three subjects (3.8%) classified as negative for COVID‐19. The sensitivity and specificity percentages for IgM or IgG antibodies were 92.9% (95% CI: 84.1‐97.6) and 96.2% (95% CI: 89.3‐99.2), respectively, with 95.6% PPV and 93.8% NPV. The PPV rapidly improved with increasing disease prevalence from 19.8% to 96.1% in the presence of either IgM or IgG, while the NPV remained high with a change from 99.9% to 93.1%. The area under the ROC curve was 0.945 (95% CI: 0.903‐0.988) for subjects with either IgM or IgG positivity. In conclusion, the immunochromatography‐based COVID‐19 IgG/IgM rapid test is a useful and practical diagnostic assay for detection of COVID‐19, especially in the presence of IgM or IgG antibodies.


title: Diagnosis and Treatment of Infectious Enteritis in Neonatal and Juvenile Ruminants

text: Common causes of infectious enteritis in neonate and juvenile ruminants include viral, bacterial, and protozoal pathogens. The most common presenting sign in ruminants with infectious enteritis is diarrhea. Diagnosis of the cause of enteritis has important zoonotic and herd health implications. Severity of clinical signs with similar pathogens may differ between calves and small ruminants. Treatment of enteritis involves supportive care to correct fluid and electrolyte imbalances, provision of nutritional support for neonates, prevention and treatment of endotoxemia or sepsis, and pathogen-specific treatments when relevant and available.


title: The regulatory landscape of precision oncology laboratory medicine in the United States – Perspective on the past 5 years and considerations for future regulation

text: The regulatory landscape for precision oncology in the United States is complicated, with multiple governmental regulatory agencies with different scopes of jurisdiction. Several regulatory proposals have been introduced since the Food and Drug Administration released a draft guidance to regulate laboratory-developed tests in 2014. Key aspects of the most recent proposals and discussion of central arguments related to the regulation of precision oncology laboratory tests provides insight to stakeholders for future discussions related to regulation of laboratory tests.


title: Conducting Psychoeducational Assessments During the COVID-19 Crisis: the Danger of Good Intentions

text: Decision-makers in school psychology are presently engaged in the process of determining how to, if possible, move forward with conducting mandated psychoeducational evaluations of students in schools during the pandemic. Whereas prominent organizations within the profession (e.g., American Psychological Association, National Association of School Psychologists) have issued guidance and encouraged practitioners to delay testing, it is not clear whether that is a viable option in every jurisdiction. Accordingly, professionals are now considering the potential use of telehealth platforms to conduct assessments, in some form, as we move forward and deal with this crisis. The goal of this brief commentary is to raise some provisional limitations associated with the use of telehealth to conduct psychological assessments that we believe will have to be considered as use of these platforms is debated. Recommendations for professional practice are also provided.


Public health saves lives: sad lessons from COVID-19


title: Remdesivir investigational trials in COVID-19: a critical reappraisal

text: Abstract During outbreak of emerging disease, the most important aim is to discover an effective drug to save life. Consequently, a lot of effort are generally made by the industry to promote clinical trials with new drugs. Here we review evidence of the 8 most recent reports including 3 randomized controlled trials on the clinical efficacy of remdesivir in treating COVID-19 patient. We conclude that it is far too premature to identify remdesivir as a curative or life-saving intervention.


title: Development and evaluation of a leadership training program for public health emergency response: results from a Chinese study

text: BACKGROUND: Since the 9/11 attack and severe acute respiratory syndrome (SARS), the development of qualified and able public health leaders has become a new urgency in building the infrastructure needed to address public health emergencies. Although previous studies have reported that the training of individual leaders is an important approach, the systemic and scientific training model need further improvement and development. The purpose of this study was to develop, deliver, and evaluate a participatory leadership training program for emergency response. METHODS: Forty-one public health leaders (N = 41) from five provinces completed the entire emergency preparedness training program in China. The program was evaluated by anonymous questionnaires and semi-structured interviews held prior to training, immediately post-training and 12-month after training (Follow-up). RESULTS: The emergency preparedness training resulted in positive shifts in knowledge, self-assessment of skills for public health leaders. More than ninety-five percent of participants reported that the training model was scientific and feasible. Moreover, the response of participants in the program to the avian influenza outbreak, as well as the planned evaluations for this leadership training program, further demonstrated both the successful approaches and methods and the positive impact of this integrated leadership training initiative. CONCLUSION: The emergency preparedness training program met its aims and objectives satisfactorily, and improved the emergency capability of public health leaders. This suggests that the leadership training model was effective and feasible in improving the emergency preparedness capability.


title: Assessment of returning travellers with fever

text: Abstract Millions of people travel to the tropics each year and a significant minority of them become ill, either during their stay, or shortly after their return. Most have mild, self-limiting illnesses, but a few will have a life-threatening condition. This article outlines how to evaluate fever in the returning traveller and discusses important infection control and public health measures. A detailed travel history, which takes into account travel destinations, specific activities and risk factors in relation to the onset of symptoms, is essential for constructing a comprehensive list of differential diagnoses and guiding appropriate investigations. Importantly, all travellers returning from the tropics with a fever should be investigated for malaria, even if their return was 3 months ago or longer.


title: The Efficacy of Lockdown Against COVID-19: A Cross-Country Panel Analysis

text: BACKGROUND: There has been much debate about the effectiveness of lockdown measures in containing COVID-19, and their appropriateness given the economic and social cost they entail. To the best of our knowledge, no existing contribution to the literature has attempted to gauge the effectiveness of lockdown measures over time in a longitudinal cross-country perspective. OBJECTIVES: This paper aims to fill the gap in the literature by assessing, at an international level, the effect of lockdown measures (or the lack of such measures) on the numbers of new infections. Given this policy’s expected change in effectiveness over time, we also measure the effect of having a lockdown implemented over a given number of days (from 7 to 20 days). METHODS: We pursue our objectives by means of a quantitative panel analysis, building a longitudinal dataset with observations from countries all over the world, and estimating the impact of lockdown via feasible generalized least squares fixed effect, random effects, generalized estimating equation, and hierarchical linear models. RESULTS: Our results show that lockdown is effective in reducing the number of new cases in the countries that implement it, compared with those countries that do not. This is especially true around 10 days after the implementation of the policy. Its efficacy continues to grow up to 20 days after implementation. CONCLUSION: Results suggest that lockdown is effective in reducing the R0, i.e. the number of people infected by each infected person, and that, unlike what has been suggested in previous analyses, its efficacy continues to hold 20 days after the introduction of the policy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40258-020-00596-3) contains supplementary material, which is available to authorized users.


title: COVID-19 vaccines: breaking record times to first-in-human trials

text: The twenty-first century has come with a new era in vaccinology, in which recombinant genetic technology has contributed to setting an unprecedented fast pace in vaccine development, clearly demonstrated during the recent COVID-19 pandemic.


title: The Cholera Epidemics in Hamburg and What to Learn for COVID‐19 (SARS‐CoV‐2)

text: © 2020 International Society for Advancement of Cytometry


title: Proteomic analysis for Type I interferon antagonism of Japanese encephalitis virus NS5 protein

text: Japanese encephalitis virus (JEV) nonstructural protein 5 (NS5) exhibits a Type I interferon (IFN) antagonistic function. This study characterizes Type I IFN antagonism mechanism of NS5 protein, using proteomic approach. In human neuroblastoma cells, NS5 expression would suppress IFNβ‐induced responses, for example, expression of IFN‐stimulated genes PKR and OAS as well as STAT1 nuclear translocation and phosphorylation. Proteomic analysis showed JEV NS5 downregulating calreticulin, while upregulating cyclophilin A, HSP 60 and stress‐induced‐phosphoprotein 1. Gene silence of calreticulin raised intracellular Ca(2+) levels while inhibiting nuclear translocalization of STAT1 and NFAT‐1 in response to IFNβ, thus, indicating calreticulin downregulation linked with Type I IFN antagonism of JEV NS5 via activation of Ca(2+)/calicineurin. Calcineurin inhibitor cyclosporin A attenuated NS5‐mediated inhibition of IFNβ‐induced responses, for example, IFN‐sensitive response element driven luciferase, STAT1‐dependent PKR mRNA expression, as well as phosphorylation and nuclear translocation of STAT1. Transfection with calcineurin (vs. control) siRNA enhanced nuclear translocalization of STAT1 and upregulated PKR expression in NS5‐expressing cells in response to IFNβ. Results prove Ca(2+), calreticulin, and calcineurin involvement in STAT1‐mediated signaling as well as a key role of JEV NS5 in Type I IFN antagonism. This study offers insights into the molecular mechanism of Type I interferon antagonism by JEV NS5.


title: Prevalence of COVID-19 among patients with chronic inflammatory rheumatic diseases treated with biologic agents or small molecules: a population-based study in the first two months of COVID-19 outbreak in Italy

text: Abstract Objective: The aim of this study is to determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) among adult patients treated with biologic agents or small molecules for chronic inflammatory rheumatic diseases, in particular chronic inflammatory arthritides. Methods: To this end, a population-based study, in the province of Udine (466,700 inhabitants, with age > 15 years old, Friuli Venezia Giulia region, Italy) was planned. The primary outcome was the prevalence of COVID-19 in the first two months of the outbreak. All the rheumatic patients treated with biologic agents or small molecules in the last 6 months in our province were included (N=1051). Results: From February 29 to April 25, 2020, 4 adult patients (4/1051, i.e. 3.8/1000, 95% Confidence Interval 1.5-9.7/1000) were registered as swab test positive by PCR for COVID-19. Overall, a total of 47/1051 (4,5%) cases were tested for COVID-19 by PCR in the same period, and 15 of them due to symptoms compatible with COVID-19. In the general population, the prevalence was 937 cases/466700 (2/1000, 95% Confidence Interval 1.9-2.1/1000, p value=0.33, chi square test), and 20,179/466,700 (4.3%) swab tests for COVID-19 were performed.. Conclusion: The risk of COVID-19 in rheumatic patients under biologic agents or small molecules does not appear different from that observed in the general population. Patients should be informed to safely proceed with their treatment and follow the rules for self-protection to COVID-19.


title: Atlas of coronavirus replicase structure

text: Abstract The international response to SARS-CoV has produced an outstanding number of protein structures in a very short time. This review summarizes the findings of functional and structural studies including those derived from cryoelectron microscopy, small angle X-ray scattering, NMR spectroscopy, and X-ray crystallography, and incorporates bioinformatics predictions where no structural data is available. Structures that shed light on the function and biological roles of the proteins in viral replication and pathogenesis are highlighted. The high percentage of novel protein folds identified among SARS-CoV proteins is discussed.