title: Evaluation of oral administration of bacteriophages to neonatal calves: Phage survival and impact on fecal Escherichia coli

text: Abstract Diarrhea is an important cause of morbidity and mortality in neonatal calves. Several enteropathogens are associated with diarrhea in young calves, with Enterotoxigenic Escherichia coli (ETEC) infection being the most common type of colibacillosis. The rise of antibiotic resistance in a number of medically important bacterial pathogens has revived interest in the use of bacteriophages as anti-bacterial therapeutic agents. Here we describe the results of a randomized, placebo-controlled, double-blinded study designed to evaluate the effect of an oral bacteriophage cocktail on fecal E. coli colony-forming units (CFU). Ten calves were enrolled in the study to either the bacteriophage group or the placebo group for 22 feedings. Calves in the bacteriophage treatment group (n=6) received a total of 106 plaque-forming units (PFU) (volume=5ml) of each of four bacteriophages while the placebo group (n=4) received only phosphate-buffered saline (5ml). Fresh fecal samples and blood samples were collected daily from each calf and analyzed for bacterial count and presence of bacteriophage. E. coli-infecting phages were recovered from all phage-treated calves at concentrations of 10² to 10³ PFU per gram of rectal contents, but none was detected in serum. Phage treatment caused a reduction in fecal E. coli when compared to the control group: the mean log CFU for the placebo-treated group was 9.25 (SE=0.42) versus 9.11 (SE=0.34) for the phage-treated group, but the difference was not statistically significant.


title: Response and role of palliative care during the COVID-19 pandemic: A national telephone survey of hospices in Italy

text: BACKGROUND: Palliative care is an important component of health care in pandemics, contributing to symptom control, psychological support, and supporting triage and complex decision making. AIM: To examine preparedness for, and impact of, the COVID-19 pandemic on hospices in Italy to inform the response in other countries. DESIGN: Cross-sectional telephone survey, in March 2020. SETTING: Italian hospices, purposively sampled according to COVID-19 regional prevalence categorised as high (>25), medium (15–25) and low prevalence (<15) COVID-19 cases per 100,000 inhabitants. A brief questionnaire was developed to guide the interviews. Analysis was descriptive. RESULTS: Seven high, five medium and four low prevalence hospices provided data. Two high prevalence hospices had experienced COVID-19 cases among both patients and staff. All hospices had implemented policy changes, and several had rapidly implemented changes in practice including transfer of staff from inpatient to community settings, change in admission criteria and daily telephone support for families. Concerns included scarcity of personal protective equipment, a lack of hospice-specific guidance on COVID-19, anxiety about needing to care for children and other relatives, and poor integration of palliative care in the acute planning response. CONCLUSION: The hospice sector is capable of responding flexibly and rapidly to the COVID-19 pandemic. Governments must urgently recognise the essential contribution of hospice and palliative care to the COVID-19 pandemic and ensure these services are integrated into the health care system response. Availability of personal protective equipment and setting-specific guidance is essential. Hospices may also need to be proactive in connecting with the acute pandemic response.


title: SARS-CoV-2 from faeces to wastewater treatment: What do we know? A review

text: Abstract SARS-CoV-2, the virus that causes COVID-19, has been found in the faeces of infected patients in numerous studies. Stool may remain positive for SARS-CoV-2, even when the respiratory tract becomes negative, and the interaction with the gastrointestinal tract poses a series of questions about wastewater and its treatments. This review aims to understand the viral load of SARS-CoV-2 in faeces and sewage and its fate in wastewater treatment plants (WWTPs). The viral load in the faeces of persons testing positive for SARS-CoV-2 was estimated at between 5·103 to 107.6 copies/mL, depending on the infection course. In the sewerage, faeces undergo dilution and viral load decreases considerably in the wastewater entering a WWTP with a range from 2 copies/100 mL to 3·103 copies/mL, depending on the level of the epidemic. Monitoring of SARS-CoV-2 in sewage, although no evidence of COVID-19 transmission has been found via this route, could be advantageously exploited as an early warning of outbreaks. Preliminary studies on WBE seem promising; but high uncertainty of viral loads in wastewater and faeces remains, and further research is needed. The detection of SARS-CoV-2 in sewage, based on RNA sequences and RT-PCR, requires a shared approach on sample pre-treatment and on-site collection to ensure comparable results. The finding of viral RNA in stools does not imply that the virus is viable and infectious. Viability of CoVs such as SARS-CoV-2 decreases in wastewater - due to temperature, pH, solids, micropollutants - but high inactivation in WWTPs can be obtained only by using disinfection (free chlorine, UVC light). A reduction in the quantity of disinfectants can be obtained by implementing Membrane-Bioreactors with ultrafiltration to separate SARS-CoV-2 virions with a size of 60–140 nm. In sludge treatment, thermophilic digestion is effective, based on the general consensus that CoVs are highly sensitive to increased temperatures.


title: Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice

text: The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN-γ production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.


title: In vivo detection of circulating tumour cell clusters by photodiagnostic spectroscopy

text: Abstract Background We demonstrate a new diagnostic method, the Photodiagnostic Infrared Spectroscoppy (PDIS), which is able to detect circulating tumor clusters and circulating tumor cells in the circulatory system. Methods The PDIS method is based on photodiagnostic physics and high resolution spectroscopy and is using calibrated spectroscopic data for the diagnostic analysis of the blood screening spectra. Using Confocal Laser Scanning Mikcroscopy the Indocyangreen-uptake of different cell lines of breast cancer cells is studied. Results The PDIS supplies calibrated diagnostic data about the presence or absence of CTCs and CTC clusters in the bloodstream with a sensitivity of 98 %. Therefore, the PDIS is suited to control the blood of cancer patients with respect of CTC and CTC clusters with an resolution of one CTC and one CTC cluster per blood volume. PDIS distinguishes the different phenotypes of CTC clusters. Conclusion Circulating tumor cell slusters play a key role in the metastatic process and are formed only in solid tumors, they are appropriate objects to validate cancer treatments and to recognice cancer formation. The PDIS is a calibrated diagnostic method which allows to evaluate the results of solid tumor treatments and of chemotherapy treatments and to optimize the individual cancer treatment strategies.


title: A Quantitative and Qualitative Analysis of the COVID–19 Pandemic Model

text: Global efforts around the world are focused on to discuss several health care strategies for minimizing the impact of the new coronavirus (COVID-19) on the community. As it is clear that this virus becomes a public health threat and spreading easily among individuals. Mathematical models with computational simulations are effective tools that help global efforts to estimate key transmission parameters and further improvements for controlling this disease. This is an infectious disease and can be modeled as a system of non-linear differential equations with reaction rates. This work reviews and develops some suggested models for the COVID-19 that can address important questions about global health care and suggest important notes. Then, we suggest an updated model that includes a system of differential equations with transmission parameters. Some key computational simulations and sensitivity analysis are investigated. Also, the local sensitivities for each model state concerning the model parameters are computed using three different techniques: non-normalizations, half normalizations, and full normalizations. Results based on the computational simulations show that the model dynamics are significantly changed for different key model parameters. Interestingly, we identify that transition rates between asymptomatic infected with both reported and unreported symptomatic infected individuals are very sensitive parameters concerning model variables in spreading this disease. This helps international efforts to reduce the number of infected individuals from the disease and to prevent the propagation of new coronavirus more widely on the community. Another novelty of this paper is the identification of the critical model parameters, which makes it easy to be used by biologists with less knowledge of mathematical modeling and also facilitates the improvement of the model for future development theoretically and practically.


title: TNF-alpha, produced by feline infectious peritonitis virus (FIPV)-infected macrophages, upregulates expression of type II FIPV receptor feline aminopeptidase N in feline macrophages

text: Abstract The pathogenicity of feline infectious peritonitis virus (FIPV) is known to depend on macrophage tropism, and this macrophage infection is enhanced by mediation via anti-S antibody (antibody-dependent enhancement, ADE). In this study, we found that TNF-alpha production was increased with viral replication in macrophages inoculated with a mixture of FIPV and anti-S antibody, and demonstrated that this culture supernatant had feline PBMC apoptosis-inducing activity. We also demonstrated that the expression level of the FIPV virus receptor, feline aminopeptidase N (fAPN), was increased in macrophages of FIP cats. For upregulation of TNF-alpha and fAPN in macrophages, viral replication in macrophages is necessary, and their expressions were increased by ADE of FIPV infection. It was demonstrated that a heat-resistant fAPN-inducing factor was present in the culture supernatant of FIPV-infected macrophages, and this factor was TNF-alpha: fAPN expression was upregulated in recombinant feline TNF-alpha-treated macrophages, and FIPV infectivity was increased in these macrophages. These findings suggested that FIPV replication in macrophages increases TNF-alpha production in macrophages, and the produced TNF-alpha acts and upregulates fAPN expression, increasing FIPV sensitivity.


title: High Fluorescent Lymphocytes Are Increased in COVID‐19 Patients

text: Since the outbreak of SARS‐CoV‐2 in December 2019, the etiology of Coronavirus Disease 2019 (COVID‐19) has spread to most of the world within months. The understanding of pathomechanism of SARS‐CoV‐2 is extremely limited.


title: Surveillance of Community Outbreaks of Respiratory Tract Infections Based on House-Call Visits in the Metropolitan Area of Athens, Greece

text: BACKGROUND: The traditional Serfling-type approach for influenza-like illness surveillance requires long historical time-series. We retrospectively evaluated the use of recent, short, historical time-series for recognizing the onset of community outbreaks of respiratory tract infections (RTIs). METHODS: The data used referred to the proportion of diagnoses for upper or lower RTIs to total diagnoses for house-call visits, performed by a private network of medical specialists (SOS Doctors) in the metropolitan area of Athens, Greece, between January 01, 2000 and October 12, 2008. The reference standard classification of the observations was obtained by generating epidemic thresholds after analyzing the full 9-year period. We evaluated two different alert generating methods [simple regression and cumulative sum (CUSUM), respectively], under a range of input parameters, using data for the previous running 4–6 week period. These methods were applied if the previous weeks contained non-aberrant observations. RESULTS: We found that the CUSUM model with a specific set of parameters performed marginally better than simple regression for both groups. The best results (sensitivity, specificity) for simple regression and CUSUM models for upper RTIs were (1.00, 0.82) and (0.94, 0.93) respectively. Corresponding results for lower RTIs were (1.00, 0.80) and (0.93, 0.91) respectively. CONCLUSIONS: Short-term data for house-call visits can be used rather reliably to identify respiratory tract outbreaks in the community using simple regression and CUSUM methods. Such surveillance models could be particularly useful when a large historical database is either unavailable or inaccurate and, thus, traditional methods are not optimal.


title: Individual or Common Good? Voluntary Data Sharing to Inform Disease Surveillance Systems in Food Animals

text: Livestock producers have traditionally been reluctant to share information related to their business, including data on health status of their animals, which, sometimes, has impaired the ability to implement surveillance programs. However, during the last decade, swine producers in the United States (US) and other countries have voluntarily begun to share data for the control and elimination of specific infectious diseases, such as the porcine reproductive and respiratory syndrome virus (PRRSv). Those surveillance programs have played a pivotal role in bringing producers and veterinarians together for the benefit of the industry. Examples of situations in which producers have decided to voluntarily share data for extended periods of time to support applied research and, ultimately, disease control in the absence of a regulatory framework have rarely been documented in the peer-reviewed literature. Here, we provide evidence of a national program for voluntary sharing of disease status data that has helped the implementation of surveillance activities that, ultimately, allowed the generation of critically important scientific information to better support disease control activities. Altogether, this effort has supported, and is supporting, the design and implementation of prevention and control approaches for the most economically devastating swine disease affecting the US. The program, which has been voluntarily sustained and supported over an extended period of time by the swine industry in the absence of any regulatory framework and that includes data on approximately 50% of the sow population in the US, represents a unique example of a livestock industry self-organized surveillance program to generate scientific-driven solutions for emerging swine health issues in North America.


title: Enhancement of cytotoxicity against Vero E6 cells persistently infected with SARS-CoV by Mycoplasma fermentans

text: We previously reported that cells with persistent severe acute respiratory syndrome coronavirus (SARS-CoV) infection were established after apoptotic events. In the present study, we investigated the cytopathic effects of dual infection with SARS-CoV and Mycoplasma fermentans on Vero E6 cells. Dual infection completely killed cells and prevented the establishment of persistent SARS-CoV infection. M. fermentans induced inhibition of cell proliferation, but the cells remained alive. Apoptosis was induced easily in M. fermentans-infected cells, indicating that they were primed for apoptosis. These results indicated that M. fermentans enhances apoptosis in surviving cells that have escaped from SARS-CoV-induced apoptosis.


title: Catatonia and the immune system: a review

text: Summary Catatonia is a psychomotor disorder featuring stupor, posturing, and echophenomena. This Series paper examines the evidence for immune dysregulation in catatonia. Activation of the innate immune system is associated with mutism, withdrawal, and psychomotor retardation, which constitute the neurovegetative features of catatonia. Evidence is sparse and conflicting for acute-phase activation in catatonia, and whether this feature is secondary to immobility is unclear. Various viral, bacterial, and parasitic infections have been associated with catatonia, but it is primarily linked to CNS infections. The most common cause of autoimmune catatonia is N-methyl-D-aspartate receptor (NMDAR) encephalitis, which can account for the full spectrum of catatonic features. Autoimmunity appears to cause catatonia less by systemic inflammation than by the downstream effects of specific actions on extracellular antigens. The specific association with NMDAR encephalitis supports a hypothesis of glutamatergic hypofunction in catatonia.


title: Etiology of acute respiratory disease in fattening pigs in Finland

text: BACKGROUND: The objective of our study was to clinically and etiologically investigate acute outbreaks of respiratory disease in Finland. Our study also aimed to evaluate the clinical use of various methods in diagnosing respiratory infections under field conditions and to describe the antimicrobial resistance profile of the main bacterial pathogen(s) found during the study. METHODS: A total of 20 case herds having finishing pigs showing acute respiratory symptoms and eight control herds showing no clinical signs suggesting of respiratory problems were enrolled in the study. Researchers visited each herd twice, examining and bleeding 20 pigs per herd. In addition, nasal swab samples were taken from 20 pigs and three pigs per case herd were necropsied during the first visit. Serology was used to detect Actinobacillus pleuropneumoniae (APP), swine influenza virus (SIV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine respiratory coronavirus (PRCV) and Mycoplasma hyopneumoniae antibodies. Polymerase chain reaction (PCR) was used to investigate the presence of porcine circovirus type 2 (PCV2) in serum and SIV in the nasal and lung samples. Pathology and bacteriology, including antimicrobial resistance determination, were performed on lung samples obtained from the field necropsies. RESULTS: According to the pathology and bacteriology of the lung samples, APP and Ascaris suum were the main causes of respiratory outbreaks in 14 and three herds respectively, while the clinical signs in three other herds had a miscellaneous etiology. SIV, APP and PCV2 caused concurrent infections in certain herds but they were detected serologically or with PCR also in control herds, suggesting possible subclinical infections. APP was isolated from 16 (80%) case herds. Marked resistance was observed against tetracycline for APP, some resistance was detected against trimethoprim/sulfamethoxazole, ampicillin and penicillin, and no resistance against florfenicol, enrofloxacin, tulathromycin or tiamulin was found. Serology, even from paired serum samples, gave inconclusive results for acute APP infection diagnosis. CONCLUSIONS: APP was the most common cause for acute respiratory outbreaks in our study. SIV, A. suum, PCV2 and certain opportunistic bacteria were also detected during the outbreaks; however, viral pathogens appeared less important than bacteria. Necropsies supplemented with microbiology were the most efficient diagnostic methods in characterizing the studied outbreaks.


title: Native and exotic plants with edible fleshy fruits utilized in Patagonia and their role as sources of local functional foods

text: BACKGROUND: Traditionally part of the human diet, plants with edible fleshy fruits (PEFF) contain bioactive components that may exert physiological effects beyond nutrition, promoting human health and well-being. Focusing on their food-medicine functionality, different ways of using PEFF were studied in a cross-sectional way using two approaches: a bibliographical survey and an ethnobotanical case study in a rural community of Patagonia, Argentina. METHODS: A total of 42 studies were selected for the bibliographical review. The case study was carried out with 80% of the families inhabiting the rural community of Cuyín Manzano, using free listing, interviews, and participant observation. In both cases we analyzed species richness and use patterns through the edible consensus and functional consensus indices. Local foods, ailments, medicines and drug plants were also registered. RESULTS: The review identified 73 PEFF, the majority of which (78%) were native species, some with the highest use consensus. PEFF were used in 162 different local foods, but mainly as fresh fruit. Of the total, 42% were used in a functional way, in 54 different medicines. The principal functional native species identified in the review were Aristotelia chilensis and Berberis microphylla. In the case study 20 PEFF were in current use (50% were native), and consensus values were similar for native and exotic species. These were used in 44 different local foods, mainly as fresh fruit. Only 30% were recognized for their functional value by inhabitants (mainly as gastrointestinal and respiratory treatments). The species with the highest functional consensus were the exotic Sambucus nigra and Rosa rubiginosa, followed by the native A. chilensis, Ribes magellanicum and B. microphylla. Infusions also constituted important local functional foods. CONCLUSIONS: This survey highlights the importance of studying the different local functional foods to depict the biocultural diversity of a human society. The preparation of different beverages and herbal medicines was relevant, and would be a promising subject to investigate in the future. The living heritage of PEFF appears to have undergone hybridization processes, such that exotic species play an increasingly significant role.


title: Presence of Vaccine-Derived Newcastle Disease Viruses in Wild Birds

text: Our study demonstrates the repeated isolation of vaccine-derived Newcastle disease viruses from different species of wild birds across four continents from 1997 through 2014. The data indicate that at least 17 species from ten avian orders occupying different habitats excrete vaccine-derived Newcastle disease viruses. The most frequently reported isolates were detected among individuals in the order Columbiformes (n = 23), followed in frequency by the order Anseriformes (n = 13). Samples were isolated from both free-ranging (n = 47) and wild birds kept in captivity (n = 7). The number of recovered vaccine-derived viruses corresponded with the most widely utilized vaccines, LaSota (n = 28) and Hitchner B1 (n = 19). Other detected vaccine-derived viruses resembled the PHY-LMV2 and V4 vaccines, with five and two cases, respectively. These results and the ubiquitous and synanthropic nature of wild pigeons highlight their potential role as indicator species for the presence of Newcastle disease virus of low virulence in the environment. The reverse spillover of live agents from domestic animals to wildlife as a result of the expansion of livestock industries employing massive amounts of live virus vaccines represent an underappreciated and poorly studied effect of human activity on wildlife.


One Lung Ventilation: A simple technique to reduce air contamination during the COVID-19 pandemic


Virtual Parkinson Disease Support Groups in the COVID‐19 Era: Social Connection in the Time of Social Distancing


Viroporin Activity of SARS-CoV E Protein


title: New Alphacoronavirus in Mystacina tuberculata Bats, New Zealand

text: Because of recent interest in bats as reservoirs of emerging diseases, we investigated the presence of viruses in Mystacina tuberculata bats in New Zealand. A novel alphacoronavirus sequence was detected in guano from roosts of M. tuberculata bats in pristine indigenous forest on a remote offshore island (Codfish Island).


title: Guidance and Patient Instructions for Proning and Repositioning of Awake, Non‐Intubated COVID‐19 Patients

text: Prior studies on proning awake, non‐intubated patients with hypoxemic acute respiratory failure, as well as evolving study of similar COVID‐19 patients, coupled with experience and dramatic anecdotal evidence from the COVID‐19 pandemic, suggest the importance of proning all such patients with COVID‐19 to improve oxygenation and reduce respiratory effort. Literature and experience from healthcare teams in the midst of the pandemic suggest that any COVID‐19 patients with respiratory compromise severe enough to warrant admission should be considered for proning. We additionally suggest these patients should be considered for proning as well as ongoing patient re‐positioning (e.g. right lateral decubitus, seated, and left lateral decubitus positions). Figure 1 represents the proning and positioning instructions developed at New York City Health + Hospitals/Elmhurst, a large, inner‐city, tertiary public hospital in the epicenter of the COVID‐19 pandemic in New York City, and later adapted and utilized at facilities across the United States.


title: Treating the SARS‐CoV‐2–positive patient with cancer: A proposal for a pragmatic and transparent ethical process

text: The treatment of patients with cancer who test positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) poses unique challenges. In this commentary, the authors describe the ethical rationale and implementation details for the creation of a novel, multidisciplinary treatment prioritization committee, including physicians, frontline staff, an ethicist, and an infectious disease expert. Organizational obligations to health care workers also are discussed. The treatment prioritization committee sets a threshold of acceptable harm to patients from decreased cancer control that is justified to reduce risk to staff. The creation of an ethical, consistent, and transparent decision‐making process involving such frontline stakeholders is essential as departments across the country are faced with decisions regarding the treatment of SARS‐CoV‐2–positive patients with cancer.


docid: usknmlqg

title: Efficacy of a Virus-Like Nanoparticle As Treatment for a Chronic Viral Infection Is Hindered by IRAK1 Regulation and Antibody Interference

text: Although vaccination has been an effective way of preventing infections ever since the eighteenth century, the generation of therapeutic vaccines and immunotherapies is still a work in progress. A number of challenges impede the development of these therapeutic approaches such as safety issues related to the administration of whole pathogens whether attenuated or inactivated. One safe alternative to classical vaccination methods gaining recognition is the use of nanoparticles, whether synthetic or naturally derived. We have recently demonstrated that the papaya mosaic virus (PapMV)-like nanoparticle can be used as a prophylactic vaccine against various viral and bacterial infections through the induction of protective humoral and cellular immune responses. Moreover, PapMV is also very efficient when used as an immune adjuvant in an immunotherapeutic setting at slowing down the growth of aggressive mouse melanoma tumors in a type I interferon (IFN-I)-dependent manner. In the present study, we were interested in exploiting the capacity of PapMV of inducing robust IFN-I production as treatment for the chronic viral infection model lymphocytic choriomeningitis virus (LCMV) clone 13 (Cl13). Treatment of LCMV Cl13-infected mice with two systemic administrations of PapMV was ineffective, as shown by the lack of changes in viral titers and immune response to LCMV following treatment. Moreover, IFN-α production following PapMV administration was almost completely abolished in LCMV-infected mice. To better isolate the mechanisms at play, we determined the influence of a pretreatment with PapMV on secondary PapMV administration, therefore eliminating potential variables emanating from the infection. Pretreatment with PapMV led to the same outcome as an LCMV infection in that IFN-α production following secondary PapMV immunization was abrogated for up to 50 days while immune activation was also dramatically impaired. We showed that two distinct and overlapping mechanisms were responsible for this outcome. While short-term inhibition was partially the result of interleukin-1 receptor-associated kinase 1 degradation, a crucial component of the toll-like receptor 7 signaling pathway, long-term inhibition was mainly due to interference by PapMV-specific antibodies. Thus, we identified a possible pitfall in the use of virus-like particles for the systemic treatment of chronic viral infections and discuss mitigating alternatives to circumvent these potential problems.


title: Reverse transcription recombinase polymerase amplification with lateral flow dipsticks for detection of influenza A virus and subtyping of H1 and H3

text: Abstract Three reverse transcription recombinase polymerase amplification assays with lateral flow dipsticks (RT-RPA-LFD) were developed for identification of the matrix and hemagglutinin (HA) genes to detect influenza A virus and distinguish subtypes H1 and H3. Assessment of the assays’ specificity showed that there was no cross-reactivity with other targets. Their limits of detection were 123.6 copies per reaction for the matrix gene, 677.1 copies per reaction for the H1 HA gene, and 112.2 copies/reaction for the H3 HA gene. Of 111 samples tested by RT-RPA-LFD assays, 27 were positive for influenza A virus, 14 were positive for H1, and 10 were positive for H3. Compared to the results obtained from real-time RT-PCR assays, the sensitivity of RT-RPA-LFD assays was 75%, 93.33% and 71.43% for the matrix, H1, and H3, with 100% specificity. The sensitivity of RT-RPA-LFD assays is lower than that of real-time RT-PCR, comparable or better than that of conventional RT-PCR, and much better than that of RIDTs. In conclusion, these assays offer an efficient and reliable tool for identification and subtyping of influenza A virus (subtype H1 and H3) in the resource-limited setting.


Pembina to defer PDH/PP project in Canada; cuts CapEx


title: Ficus septica plant extracts for treating Dengue virus in vitro

text: Dengue virus types 1-4 (DENV-1-4) are positive-strand RNA viruses with an envelope that belongs to the Flaviviridae. DENV infection threatens human health worldwide. However, other than supportive treatments, no specific therapy is available for the infection. In order to discover novel medicine against DENV, we tested 59 crude extracts, without cytotoxicity, from 23 plants in vitro; immunofluorescence assay revealed that the methanol extracts of fruit, heartwood, leaves and stem from Ficus septica Burm. f. had a promising anti-DENV-1 and DENV-2 effect. However, infection with the non-envelope picornavirus, Aichi virus, was not inhibited by treatment with F. septica extracts. F. septica may be a candidate antiviral drug against an enveloped virus such as DENV.


title: Transfusion-transmitted infections

text: Although the risk of transfusion-transmitted infections today is lower than ever, the supply of safe blood products remains subject to contamination with known and yet to be identified human pathogens. Only continuous improvement and implementation of donor selection, sensitive screening tests and effective inactivation procedures can ensure the elimination, or at least reduction, of the risk of acquiring transfusion transmitted infections. In addition, ongoing education and up-to-date information regarding infectious agents that are potentially transmitted via blood components is necessary to promote the reporting of adverse events, an important component of transfusion transmitted disease surveillance. Thus, the collaboration of all parties involved in transfusion medicine, including national haemovigilance systems, is crucial for protecting a secure blood product supply from known and emerging blood-borne pathogens.


title: Oseltamivir for coronavirus illness: post-hoc exploratory analysis of an open-label, pragmatic, randomised controlled trial in European primary care from 2016 to 2018

text: BACKGROUND: Patients infected with the novel coronavirus (SARS-CoV-2) are being treated empirically with oseltamivir, but there is little evidence from randomised controlled trials to support the treatment of coronavirus infections with oseltamivir. AIM: To determine whether adding oseltamivir to usual care reduces time to recovery in symptomatic patients who have tested positive for coronavirus (not including SARS-CoV-2). DESIGN AND SETTING: Exploratory analysis of data from an open-label, pragmatic, randomised controlled trial during three influenza seasons, from 2016 to 2018, in primary care research networks, in 15 European countries. METHOD: Patients aged ≥1 year presenting to primary care with influenza-like illness (ILI), and who tested positive for coronavirus (not including SARS-CoV-2), were randomised to usual care or usual care plus oseltamivir. The primary outcome was time to recovery defined as a return to usual activities, with minor or absent fever, headache, and muscle ache. RESULTS: Coronaviruses (CoV-229E, CoV-OC43, CoV-KU1 and CoV-NL63) were identified in 308 (9%) out of 3266 randomised participants in the trial; 153 of these were allocated to usual care and 155 to usual care plus oseltamivir; the primary outcome was ascertained in 136 and 147 participants, respectively. The median time to recovery was shorter in patients randomised to oseltamivir: 4 days (interquartile range [IQR] 3–6) versus 5 days (IQR 3–8; hazard ratio 1.31; 95% confidence interval = 1.03 to 1.66; P = 0.026). CONCLUSION: Primary care patients with ILI testing positive for coronavirus (not including SARS-CoV-2) recovered sooner when oseltamivir was added to usual care compared with usual care alone. This may be of relevance to the primary care management of COVID-19.


title: Yeast surface display-based microfluidic immunoassay

text: Abstract In this paper, we present a new microfluidic immunoassay platform, which is based on the synergistic combination of the yeast surface display (YSD) technique and the microfluidic technology. Utilizing the YSD technique, antigens specific to the target antibody are displayed on the surface of engineered yeast cells with intracellular fluorescent proteins. The displayed antigens are then used for the detection of the target antibody, with the yeast cells as fluorescent labels. Multiplex immunoassay can be readily realized by using yeast cells expressing different intracellular fluorescent proteins to display different antigens. The implementation of this YSD-based immunoassay on the microfluidic platform eliminates the need for the bulky, complex and expensive flow cytometer. To improve the detection sensitivity and to eliminate the need for pumping, a functionalized micro pillar array (MPA) is incorporated in the microfluidic chip, resulting in a detection limit of 5ng/mL (or 1ng in terms of amount) and enhanced compatibility with practical applications such as clinical biopsy. This new platform has a high potential to be integrated into microfluidic detection systems to enable portable diagnostics in the future.


Use of antimalarial drugs in the treatment of COVID-19: A window of opportunity?


title: Rapid typing of influenza viruses using super high-speed quantitative real-time PCR

text: Abstract The development of a rapid and sensitive system for detecting influenza viruses is a high priority for controlling future epidemics and pandemics. Quantitative real-time PCR is often used for detecting various kinds of viruses; however, it requires more than 2h per run. Detection assays were performed with super high-speed RT-PCR (SHRT-PCR) developed according to a newly designed heating system. The new method uses a high-speed reaction (18s/cycle; 40 cycles in less than 20min) for typing influenza viruses. The detection limit of SHRT-PCR was 1 copy/reaction and 10−1 plaque-forming unit/reaction for viruses in culture supernatants during 20min. Using SHRT-PCR, 86 strains of influenza viruses isolated by the Tokyo Metropolitan Institute of Public Health were tested; the results showed 100% sensitivity and specificity for each influenza A and B virus, and swine-origin influenza virus. Twenty-seven swabs collected from the pharyngeal mucosa of outpatients were also tested, showing positive signs for influenza virus on an immunochromatographic assay; the results between SHRT-PCR and immunochromatography exhibited 100% agreement for both positive and negative results. The rapid reaction time and high sensitivity of SHRT-PCR makes this technique well suited for monitoring epidemics and pre-pandemic influenza outbreaks.


title: Possible special needs for mental online support in female and male health care workers during the COVID‐19

text: In their article Wu and colleagues, similarly to other authors, present the effects of stress on medical staff during the COVID-19 pandemic as an unprecedented challenge for all communities. Their observation is within current literature trends, which identify 7 population subgroups affected by the psychosocial consequences of the COVID-19: general population affected by restrictive measures, people subjected to quarantine, positive for the virus (isolated/hospitalized), health care personnel, relatives of persons who died, and mentally ill patients. This article is protected by copyright. All rights reserved.


title: Avian H11 influenza virus isolated from domestic poultry in a Colombian live animal market

text: Live animal markets (LAMs) are an essential source of food and trade in Latin American countries; however, they can also serve as ‘hotbeds' for the emergence and potential spillover of avian influenza viruses (AIV). Despite extensive knowledge of AIV in Asian LAMs, little is known about the prevalence South American LAMs. To fill this gap in knowledge, active surveillance was carried out at the major LAM in Medellin, Colombia between February and September 2015. During this period, overall prevalence in the market was 2.67% and a North American origin H11N2 AIV most similar to a virus isolated from Chilean shorebirds asymptomatically spread through multiple bird species in the market resulting in 17.0% positivity at peak of infection. Phenotypically, the H11 viruses displayed no known molecular markers associated with increased virulence in birds or mammals, had α2,3-sialic acid binding preference, and caused minimal replication in vitro and little morbidity in vivo. However, the Colombian H11N2 virus replicated and transmitted effectively in chickens explaining the spread throughout the market. Genetic similarity to H11 viruses isolated from North and South American shorebirds suggest that the LAM occurrence may have resulted from a wild bird to domestic poultry spillover event. The ability to spread in domestic poultry as well as potential for human infection by H11 viruses highlight the need for enhanced AIV surveillance in South America in both avian species and humans.


title: Can an Infectious Disease Genomics Project Predict and Prevent the Next Pandemic?

text: Infectious diseases need a globally coordinated genomic-based movement linking sequencing efforts to development of response tools to mitigate the impact of existing and emerging threats.


title: Prolonged depletion of circulating CD4+ T lymphocytes and acute monocytosis after pantropic canine coronavirus infection in dogs

text: Abstract A hypervirulent strain (CB/05) of canine coronavirus was employed to infect oronasally 11-week-old pups. Peripheral blood monocytes (CD14+), T lymphocytes (CD4+ and CD8+) and B lymphocytes (CD21+) were studied by flow cytometry within 5 days post-infection (p.i.) and at later time points. Infection with CB/05 resulted in a profound depletion of T cells and a slight loss of B cells in the first week p.i. In particular, while the CD8+ and the B lymphocytes returned to baseline levels by day 7 p.i., the CD4+ T cells remained significantly low until day 30 p.i. and recovered completely only at day 60 p.i. Monocytosis was also observed after CB/05 infection with a peak at day 5 p.i. The prolonged depletion of peripheral CD4+ T cells did not alter the levels of serum IgG or IgM. The impact of CB/05 infection on the immune performance of infected pups is discussed.


title: Pneumatosis intestinalis in COVID-19

text: INTRODUCTION: COVID-19 is a respiratory illness due to novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), described in December 2019 in Wuhan (China) and rapidly evolved into a pandemic. Gastrointestinal (GI) tract can also be involved. CASE PRESENTATION: A 44-year-old man was hospitalised for COVID-19-associated pneumonia. A rapid recovery of respiratory and general symptoms was observed after 1 week of treatment with lopinavir/ritonavir plus hydroxychloroquine and broad-spectrum antibiotics (piperacillin–tazobactam plus teicoplanin). No GI symptoms were reported during hospitalisation, but a lung contrast-enhancement CT (CE-CT) excluding thromboembolism showed, as collateral finding, intraperitoneal free bubbles not present on a previous CT examination; the subsequent abdominal CE-CT described pneumatosis intestinalis (PI) involving the caecum and the right colon. Ciprofloxacin plus metronidazole was started, and the 2-week follow-up CT showed the complete resolution of PI. DISCUSSION: The pathogenesis of PI is poorly understood. PI involving the caecum and right colon has been described for HIV and Cytomegalovirus infections, but, to our best knowledge, never before in COVID-19. We hypothesise a multifactorial aetiopathogenesis for PI, with a possible role of the bowel wall damage and microbiota impairment due to SARS-CoV-2 infection, and we suggest a conservative management in the absence of symptoms.


title: Management of bronchiolitis

text: Abstract Bronchiolitis is the commonest cause of hospital admission in infancy. Severity varies from mild and self-limiting through to respiratory failure requiring intensive care and ventilation. Many viruses cause bronchiolitis, the commonest being respiratory syncytial virus (RSV). Supportive care is the mainstay of treatment, with emphasis on fluid replacement and oxygen therapy. Agents with evidence of no benefit in acute bronchiolitis include β2 agonists, ipratropium, montelukast, corticosteroids, antiviral agents such as ribavirin or RSV immunoglobulin, physiotherapy, nebulized deoxyribonuclease or antibiotics. It is possible that nebulized epinephrine has a small short-term effect, and that nebulized 3% hypertonic saline administered with a bronchodilator may decrease length of stay in hospital. Preventative strategies such as RSV immunoglobulin or the anti-RSV monoclonal antibody palivizumab can decrease disease severity.


title: Recommendations for Hospital-Based Physical Therapists Managing Patients With COVID-19

text: OBJECTIVE: The COVID-19 pandemic is rapidly evolving and has led to increased numbers of hospitalizations worldwide. Hospitalized patients with COVID-19 experience a variety of symptoms, including fever, muscle pain, tiredness, cough, and difficulty breathing. Elderly people and those with underlying health conditions are considered to be more at risk of developing severe symptoms and have a higher risk of physical deconditioning during their hospital stay. Physical therapists have an important role in supporting hospitalized patients with COVID-19 but also need to be aware of challenges when treating these patients. In line with international initiatives, this article aims to provide guidance and detailed recommendations for hospital-based physical therapists managing patients hospitalized with COVID-19 through a national approach in the Netherlands. METHODS: A pragmatic approach was used. A working group conducted a purposive scan of the literature and drafted initial recommendations based on the knowledge of symptoms in patients with COVID-19, and current practice for physical therapist management for patients hospitalized with lung disease and patients admitted to the intensive care unit (ICU). An expert group of hospital-based physical therapists in the Netherlands provided feedback on the recommendations, which were finalized when consensus was reached among the members of the working group. RESULTS: The recommendations include safety recommendations, treatment recommendations, discharge recommendations, and staffing recommendations. Treatment recommendations address 2 phases of hospitalization: when patients are critically ill and admitted to the ICU, and when patients are severely ill and admitted to the COVID ward. Physical therapist management for patients hospitalized with COVID-19 comprises elements of respiratory support and active mobilization. Respiratory support includes breathing control, thoracic expansion exercises, airway clearance techniques, and respiratory muscle strength training. Recommendations toward active mobilization include bed mobility activities, active range-of-motion exercises, active (−assisted) limb exercises, activities-of-daily-living training, transfer training, cycle ergometer, pre-gait exercises, and ambulation.


title: Delayed-type hypersensitivity response in the central nervous system during JHM virus infection requires viral specificity for protection

text: Abstract The JHM strain of mouse hepatitis virus (JHMV) elicits an I-A-restricted delayed-type hypersensitivity (DTH) response mediated by a Thy-1+, Lyt-1+, and CD4+ T cell. Adoptive transfer of these polyclonal CD4+ T cells from immunized mice prevents death in lethally infected recipients without significantly reducing virus titer in the central nervous system (CNS). These observations raise the possibility that the recruitment of mononuclear cells into the CNS may play a critical role in survival from a lethal CNS infection. Transient DTH response to nonviral antigens induced an accumulation of monocytes in the CNS that was maximal at 48 h post-challenge and virtually resolved by 5 days post-challenge. By contrast the induction of prolonged DTH responses resulted in the accumulation of a large number monocytes that persisted in the CNS for at least 5 days post-challenge. Neither type of DTH reaction suppressed virus replication or prevented death from concomitant lethal JHMV infection.


Cancer diagnosis and treatment in the COVID‐19 era


SARS Risk Perception and Preventive Measures, Singapore and Japan


title: Graft Cryopreservation Does Not Impact Overall Survival after Allogeneic Hematopoietic Cell Transplantation Using Post-Transplantation Cyclophosphamide for Graft-versus-Host Disease Prophylaxis

text: ABSTRACT The COVID-19 pandemic has created significant barriers to timely donor evaluation, cell collection, and graft transport for allogeneic hematopoietic stem cell transplantation (allo-HCT). To ensure availability of donor cells on the scheduled date of infusion, many sites now collect cryopreserved grafts before the start of pretransplantation conditioning. Post-transplantation cyclophosphamide (ptCY) is an increasingly used approach for graft-versus-host disease (GVHD) prophylaxis, but the impact of graft cryopreservation on the outcomes of allo-HCT using ptCY is not known. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared the outcomes of HCT using cryopreserved versus fresh grafts in patients undergoing HCT for hematologic malignancy with ptCY. We analyzed 274 patients with hematologic malignancy undergoing allo-HCT between 2013 and 2018 with cryopreserved grafts and ptCY. Eighteen patients received bone marrow grafts and 256 received peripheral blood stem cell grafts. These patients were matched for age, graft type, disease risk index (DRI), and propensity score with 1080 patients who underwent allo-HCT with fresh grafts. The propensity score, which is an assessment of the likelihood of receiving a fresh graft versus a cryopreserved graft, was calculated using logistic regression to account for the following: disease histology, Karnofsky Performance Score (KPS), HCT Comorbidity Index, conditioning regimen intensity, donor type, and recipient race. The primary endpoint was overall survival (OS). Secondary endpoints included acute and chronic graft-versus-host disease (GVHD), non-relapse mortality (NRM), relapse/progression and disease-free survival (DFS). Because of multiple comparisons, only P values <.01 were considered statistically significant. The 2 cohorts (cryopreserved and fresh) were similar in terms of patient age, KPS, diagnosis, DRI, HCT-CI, donor/graft source, and conditioning intensity. One-year probabilities of OS were 71.1% (95% confidence interval [CI], 68.3% to 73.8%) with fresh grafts and 70.3% (95% CI, 64.6% to 75.7%) with cryopreserved grafts (P = .81). Corresponding probabilities of OS at 2 years were 60.6% (95% CI, 57.3% to 63.8%) and 58.7% (95% CI, 51.9% to 65.4%) (P = .62). In matched-pair regression analysis, graft cryopreservation was not associated with a significantly higher risk of mortality (hazard ratio [HR] for cryopreserved versus fresh, 1.05; 95% CI, .86 to 1.29; P = .60). Similarly, rates of neutrophil recovery (HR, .91; 95% CI, .80 to 1.02; P = .12), platelet recovery (HR, .88; 95% CI, .78 to 1.00; P = .05), grade III-IV acute GVHD (HR, .78; 95% CI, .50 to 1.22; P = .27), NRM (HR, 1.16; 95% CI, .86 to 1.55; P = .32) and relapse/progression (HR, 1.21; 95% CI, .97 to 1.50; P = .09) were similar with cryopreserved grafts versus fresh grafts. There were somewhat lower rates of chronic GVHD (HR, 78; 95% CI, .61 to .99; P = .04) and DFS (HR for treatment failure, 1.19; 95% CI, 1.01 to 1.29; P = .04) with graft cryopreservation that were of marginal statistical significance after adjusting for multiple comparisons. Overall, our data indicate that graft cryopreservation does not significantly delay hematopoietic recovery, increase the risk of acute GVHD or NRM, or decrease OS after allo-HCT using ptCY.


Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis (MTB) and it represents a persistent public health threat for a number of complex biological and sociological reasons. According to the most recent Global Tuberculosis Report (2019) edited by the World Health Organization (WHO), TB is considered the ninth cause of death worldwide and the leading cause of mortality by a single infectious agent, with the highest rate of infections and death toll rate mostly concentrated in developing and low-income countries. We present here the editorial section to the Special Issue entitled “Mycobacterium tuberculosis Pathogenesis, Infection Prevention and Treatment” that includes 7 research articles and a review. The scientific contributions included in the Special Issue mainly focus on the characterization of MTB strains emerging in TB endemic countries as well as on multiple mechanisms adopted by the bacteria to resist and to adapt to antitubercular therapies.


title: New advances in our understanding of the “unique” RNase L in host pathogen interaction and immune signaling

text: Abstract Ever since the discovery of the existence of an interferon (IFN)-regulated ribonuclease, significant advances have been made in understanding the mechanism and associated regulatory effects of its action. What had been studied initially as a “unique” endoribonuclease is currently known as ribonuclease L (RNase L where “L” stands for latent). Some of the key developments include discovery of the RNase L signaling pathway, its structural characterization, and its molecular cloning. RNase L has been implicated in antiviral and antibacterial defense, as well as in hereditary prostate cancer. RNase L is activated by 2′-5′ linked oligoadenylates (2-5A), which are synthesized by the oligoadenylate synthetases (OASs), a family of IFN-regulated pathogen recognition receptors that sense double-stranded RNAs. Activated RNase L cleaves single stranded RNAs, including viral RNAs and cellular RNAs. The catalytic activity of RNase L has been found to lead into the activation of several cellular signaling pathways, including those involved in autophagy, apoptosis, IFN-β production, NLRP3 inflammasome activation leading to IL-1β secretion, inhibition of cell migration, and cell adhesion. In this review, we will highlight the newest advances in our understanding of the catalytic role of RNase L in the context of different cellular pathways and extend the scope of these findings to discussion of potential therapeutic targets for antimicrobial drug development.


title: Management of acute streptococcal pharyngitis: still the subject of controversy

text: Although most cases of acute pharyngitis are viral in origin, antibiotics are overused in its treatment. Streptococcus pyogenes (group A streptococcus, GAS), the principal bacterial pathogen of acute sore throat, is responsible for merely 5–30% of cases. Moreover, GAS pharyngitis is currently the only commonly occurring form of acute pharyngitis for which antibiotic therapy is definitely indicated. Therefore the differentiation between GAS pharyngitis and that of viral etiology is crucial. Accordingly, scientific societies as well as respected advisory bodies in Europe and North America, issued guidelines for the management of acute pharyngitis with the aim of minimizing unnecessary antibiotic prescriptions in its treatment. The aim of this review work is to confront the state of the art in acute GAS pharyngitis diagnosis and treatment with different approaches to its management represented by current European and North American guidelines. Although based on scientific evidence, international guidelines differ substantially in opinions whether GAS pharyngitis diagnosis should be based on microbiological testing, clinical algorithm or a combination of both. On the other hand, some European guidelines consider GAS pharyngitis to be a mild, self-limiting disease that does not require a specific diagnosis or antimicrobial treatment except in high-risk patients. There is an agreement among guidelines that if antibiotic therapy is indicated, phenoxymethyl penicillin should be the drug of choice to treat GAS pharyngitis.


title: Physical Disease and Resilient Outcomes: A Systematic Review of Resilience Definitions and Study Methods

text: Background Findings from physical disease resilience research may be used to develop approaches to reduce the burden of disease. However, there is no consensus on the definition and measurement of resilience in the context of physical disease. Objective The aim was to summarize the range of definitions of physical disease resilience and the approaches taken to study it in studies examining physical disease and its relationship to resilient outcomes. Methods Electronic databases were searched from inception to March 2013 for studies in which physical disease was assessed for its association with resilient outcomes. Article screening, data extraction, and quality assessment were carried out independently by 2 reviewers, with disagreements being resolved by a third reviewer. The results were combined using a narrative technique. Results Of 2280 articles, 12 met the inclusion criteria. Of these studies, 1 was of high quality, 9 were of moderate quality, and 2 were low quality. The common findings were that resilience involves maintaining healthy levels of functioning following adversity and that it is a dynamic process not a personality trait. Studies either assessed resilience based on observed outcomes or via resilience measurement scales. They either considered physical disease as an adversity leading to resilience or as a variable modifying the relationship between adversity and resilience. Conclusion This work begins building consensus as to the approach to take when defining and measuring physical disease resilience. Resilience should be considered as a dynamic process that varies across the life-course and across different domains, therefore the choice of a resilience measure should reflect this.


title: Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study

text: BACKGROUND: Assessing the burden of COVID-19 on the basis of medically attended case numbers is suboptimal given its reliance on testing strategy, changing case definitions, and disease presentation. Population-based serosurveys measuring anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies provide one method for estimating infection rates and monitoring the progression of the epidemic. Here, we estimate weekly seroprevalence of anti-SARS-CoV-2 antibodies in the population of Geneva, Switzerland, during the epidemic. METHODS: The SEROCoV-POP study is a population-based study of former participants of the Bus Santé study and their household members. We planned a series of 12 consecutive weekly serosurveys among randomly selected participants from a previous population-representative survey, and their household members aged 5 years and older. We tested each participant for anti-SARS-CoV-2-IgG antibodies using a commercially available ELISA. We estimated seroprevalence using a Bayesian logistic regression model taking into account test performance and adjusting for the age and sex of Geneva's population. Here we present results from the first 5 weeks of the study. FINDINGS: Between April 6 and May 9, 2020, we enrolled 2766 participants from 1339 households, with a demographic distribution similar to that of the canton of Geneva. In the first week, we estimated a seroprevalence of 4·8% (95% CI 2·4–8·0, n=341). The estimate increased to 8·5% (5·9–11·4, n=469) in the second week, to 10·9% (7·9–14·4, n=577) in the third week, 6·6% (4·3–9·4, n=604) in the fourth week, and 10·8% (8·2–13·9, n=775) in the fifth week. Individuals aged 5–9 years (relative risk [RR] 0·32 [95% CI 0·11–0·63]) and those older than 65 years (RR 0·50 [0·28–0·78]) had a significantly lower risk of being seropositive than those aged 20–49 years. After accounting for the time to seroconversion, we estimated that for every reported confirmed case, there were 11·6 infections in the community. INTERPRETATION: These results suggest that most of the population of Geneva remained uninfected during this wave of the pandemic, despite the high prevalence of COVID-19 in the region (5000 reported clinical cases over <2·5 months in the population of half a million people). Assuming that the presence of IgG antibodies is associated with immunity, these results highlight that the epidemic is far from coming to an end by means of fewer susceptible people in the population. Further, a significantly lower seroprevalence was observed for children aged 5–9 years and adults older than 65 years, compared with those aged 10–64 years. These results will inform countries considering the easing of restrictions aimed at curbing transmission. FUNDING: Swiss Federal Office of Public Health, Swiss School of Public Health (Corona Immunitas research program), Fondation de Bienfaisance du Groupe Pictet, Fondation Ancrage, Fondation Privée des Hôpitaux Universitaires de Genève, and Center for Emerging Viral Diseases.


title: The Psychological Impact of Epidemic and Pandemic Outbreaks on Healthcare Workers: Rapid Review of the Evidence

text: PURPOSE OF REVIEW: We aim to provide quantitative evidence on the psychological impact of epidemic/pandemic outbreaks (i.e., SARS, MERS, COVID-19, ebola, and influenza A) on healthcare workers (HCWs). RECENT FINDINGS: Forty-four studies are included in this review. Between 11 and 73.4% of HCWs, mainly including physicians, nurses, and auxiliary staff, reported post-traumatic stress symptoms during outbreaks, with symptoms lasting after 1–3 years in 10–40%. Depressive symptoms are reported in 27.5–50.7%, insomnia symptoms in 34–36.1%, and severe anxiety symptoms in 45%. General psychiatric symptoms during outbreaks have a range comprised between 17.3 and 75.3%; high levels of stress related to working are reported in 18.1 to 80.1%. Several individual and work-related features can be considered risk or protective factors, such as personality characteristics, the level of exposure to affected patients, and organizational support. SUMMARY: Empirical evidence underlines the need to address the detrimental effects of epidemic/pandemic outbreaks on HCWs’ mental health. Recommendations should include the assessment and promotion of coping strategies and resilience, special attention to frontline HCWs, provision of adequate protective supplies, and organization of online support services. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11920-020-01166-z) contains supplementary material, which is available to authorized users.


title: Analysis of S1 gene of avian infectious bronchitis virus isolated in southern China during 2011–2012

text: Sixty-two strains of avian infectious bronchitis virus (IBV) were isolated from diseased chickens at different farms in southern China during 2011–2012, and 66.1 % of the isolated strains were associated with typical nephritis. Analysis of the S1 gene sequences amplified from the 62 isolated strains together with 40 reference strains published in Genbank showed nucleotide homologies ranging from 63.5 to 99.9 % and amino acid homologies ranging from 57.9 to 100 %. Phylogenetic analysis revealed that all Chinese IBV strains were clustered into six distinct genetic groups (I–VI). Most of the isolated strains belonged to group I, and the isolation of group V strains was increased compared with an earlier period of surveillance. Current vaccine strains used in China (H120, H52, W93, and Ma5) formed the group Mass which is evolutionarily distant from Chinese isolates. Alignment of S1 amino acid sequences revealed polymorphic and diverse substitutions, insertions, and deletions, and the S1 protein of major pandemic strains contained 540 amino acids with a cleavage site sequence of HRRRR or RRF(L/S)RR. Further analysis showed that recombination events formed a new subgroup. Taken together, these findings suggest that various IBV variants were co-circulating and undergoing genetic evolution in southern China during the observation period. Therefore, long-term continuing surveillance is significantly important for prevention and control of IBV infection.


title: RFID-enabled process reengineering of closed-loop supply chains in the healthcare industry of Singapore

text: Abstract Due to an increasing global awareness of the need for sustainable development in academia and business, closed-loop supply chains in hospitals have become an important area of focus. Process reengineering in purchasing, materials management, work practices, and waste management can reduce environmental hazards and contain costs at the healthcare facilities. This paper demonstrates an application of the RFID-enabled process reengineering in sustainable healthcare system design, and presents a case study in the linens division of central sterilization services department at a Singaporean hospital using ARENA simulation.


title: COVID-19 and Multi-Organ Response

text: Abstract Since the outbreak and rapid spread of COVID-19 starting late December 2019, it has been apparent that disease prognosis has largely been influenced by multi-organ involvement. Comorbidities such as cardiovascular diseases have been the most common risk factors for severity and mortality. The hyperinflammatory response of the body, coupled with the plausible direct effects of SARS-CoV-2 on body-wide organs via ACE2, has been associated with complications of the disease. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock and multi-organ failure have precipitated death. Acknowledging the comorbidities and potential organ injuries throughout the course of COVID-19 is therefore crucial in the clinical management of patients. This paper aims to add onto the ever-emerging landscape of medical knowledge on COVID-19, encapsulating its multi-organ impact.


title: Multiplexed detection and identification of respiratory pathogens using the NxTAG® respiratory pathogen panel

text: Abstract The Luminex® NxTAG® Respiratory Pathogen Panel (NxTAG RPP) is an IVD-cleared assay for the simultaneous detection and identification of nucleic acids from 18 respiratory viruses and 2 (or 3 outside of the U.S.) atypical bacterial pathogens in nasopharyngeal swabs. Its scalability allows concurrent testing of up to 96 samples in a single batch. Nucleic acid extracted from 200 µL of raw specimen using the easyMAG® extractor is added directly to pre-plated, lyophilized bead reagents (LBRs), where multiplexed RT-PCR and hybridization to MagPlex-TAG™ microspheres occurs within a sealed reaction well using a single cycling program. Data acquisition is done on the MAGPIX® instrument which reads and sorts the reaction products directly from the sealed well following transfer of the assay plate from the thermal cycler. NxTAG is the newest innovation in bead-based nucleic acid chemistry developed by Luminex. Here we provide the detailed assay protocol and present data which describe the clinical and analytical performance characteristics of NxTAG RPP.


docid: qfquedya

title: Geospatial analysis of COVID-19 and otolaryngologists above age 60()

text: OBJECTIVE: The 2019 novel coronavirus (COVID-19) is disproportionately impacting older individuals and healthcare workers. Otolaryngologists are especially susceptible with the elevated risk of aerosolization and corresponding high viral loads. This study utilizes a geospatial analysis to illustrate the comparative risks of older otolaryngologists across the United States during the COVID-19 pandemic. METHODS AND MATERIALS: Demographic and state population data were extracted from the State Physician Workforce Reports published by the AAMC for the year 2018. A geospatial heat map of the United States was then constructed to illustrate the location of COVID-19 confirmed case counts and the distributions of ENTs over 60 years for each state. RESULTS: In 2018, out of a total of 9578 practicing U.S. ENT surgeons, 3081 were older than 60 years (32.2%). The states with the highest proportion of ENTs over 60 were Maine, Delaware, Hawaii, and Louisiana. The states with the highest ratios of confirmed COVID-19 cases to the number of total ENTs over 60 were New York, New Jersey, Massachusetts, and Michigan. CONCLUSIONS: Based on our models, New York, New Jersey, Massachusetts, and Michigan represent states where older ENTs may be the most susceptible to developing severe complications from nosocomial transmission of COVID-19 due to a combination of high COVID-19 case volumes and a high proportion of ENTs over 60 years.


title: Healthcare Utilization Monitoring System in Korea

text: OBJECTIVES: It is important to monitor the healthcare utilization of patients at the national level to make evidence-based policy decisions and manage the nation's healthcare sector. The Health Insurance Review & Assessment Service (HIRA) has run a Healthcare Utilization Monitoring System (HUMS) since 2008. The objective of this paper is to introduce HIRA's HUMS. METHODS: This study described the HUMS's system structure, capacity, functionalities, and output formats run by HIRA in the Republic of Korea. Regarding output formats, this study extracted diabetes related health insurance claims through the HUMS from August 1, 2014 to May 31, 2015. RESULTS: The HUMS has kept records of health insurance claim data for 4 years. It has a 14-terabyte hardware capacity and employs several easy-to-use programs for maintenance of the system, such as MSTR, SAS, etc. Regarding functionalities, users should input diseases codes, target periods, facility types, and types of attributes, such as the number of healthcare utilizations or healthcare costs. It also has a functionality to predict healthcare utilization and costs. When this study extracted diabetes related data, it was found that the trend of healthcare costs for the treatment of diabetes and the number of patients with diabetes were increasing. CONCLUSIONS: HIRA's HUMS works well to monitor healthcare utilization of patients at the national level. The HUMS has a high-capacity hardware infrastructure and several operational programs that allows easy access to summaries as well as details to identify contributing factors for abnormality, but it has a limitation in that there is often a time lag between the provision of healthcare to patients and the filing of health claims.


A mental health workforce crisis in China: A pre-existing treatment gap coping with the COVID-19 pandemic challanges


title: Evaluating addition of self-collected throat swabs to nasal swabs for respiratory virus detection

text: Abstract Background Early and accurate detection of respiratory viruses (RV) is important for patient management. We have previously shown that self-collected nasal swabs (NS) are feasible and as sensitive as clinician-collected nasal washes for detection of RV, but the additive benefit of self-collected throat swabs is unknown. Objectives To evaluate the added yield of self-collected nasal to throat swabs for detection of RV by PCR in patients with upper respiratory tract infection (URTI) symptoms. Study design Patients with URTI symptoms self-collected paired polyurethane foam NS and nylon flocked throat swabs and completed a symptom survey. Swabs were tested for 12 RV by real-time reverse transcription (RT)-PCR. Descriptive, McNemar's, and Wilcoxon signed rank statistical tests were used. Results 115 paired nasal and throat swabs were collected from 63 individuals, with 71/115 (62%) positive for a RV by at least one specimen, including 51 positive by both, 17 positive by NS only, and 3 positive by throat swab only. The sensitivity of NS was 96% (95%CI: 88-99) versus 76% (95% CI: 65-85) in throat swabs, p<0.001. The median PCR cycle threshold (Ct) in 51 concordant samples was lower (indicating higher viral concentration) in NS (25.1) versus throat swabs (32.0). The three samples positive only by throat swab had high Ct values (33.8, 36.2, and 38.8, all rhinovirus). Conclusion Self-collection of NS was significantly more sensitive than self collection of throat swabs for detection of RV by RT-PCR. The addition of throat sampling does not appear to increase the diagnostic load in the self-testing setting.


docid: eegyiljl

title: Rotaviral and Coronaviral Diarrhea

text: Rotaviruses and coronaviruses are very common causes of calfhood diarrhea throughout the world. Rotaviral and coronaviral infections in neonatal calves can produce a severe diarrhea of high morbidity but of variable mortality depending upon secondary bacterial infections and electrolyte imbalances. Laboratory diagnosis of rotaviral and coronaviral diarrhea is mostly done by detection of virus particles or virus antigens in fecal specimens. The sample of choice for these diagnostic tests is a fresh fecal sample collected directly from the calf as close as possible to the onset of diarrhea.


title: The actin cytoskeleton is important for rotavirus internalization and RNA genome replication

text: Abstract Numerous host factors are required for the efficient replication of rotavirus, including the activation and inactivation of several cell signaling pathways. One of the cellular structures that are reorganized during rotavirus infection is the actin cytoskeleton. In this work, we report that the dynamics of the actin microfilaments are important at different stages of the virus life cycle, specifically, during virus internalization and viral RNA synthesis at 6 h post-infection. Our results show that the actin-binding proteins alpha-actinin 4 and Diaph, as well as the Rho-family small GTPase Cdc42 are necessary for an efficient virus entry, while GTPase Rac1 is required for maximal viral RNA synthesis.


title: Beyond the gut bacterial microbiota: The gut virome

text: The gastrointestinal tract is colonized with a highly different population of bacterial, viral, ad fungal species; viruses are reported to be dominant. The composition of gut virome is closely related to dietary habits and surrounding environment. Host and their intestinal microbes live in a dynamic equilibrium and viruses stimulate a low degree of immune responses without causing symptoms (host tolerance). However, intestinal phages could lead to a rupture of eubiosis and may contribute to the shift from health to disease in humans and animals. Viral nucleic acids and other products of lysis of bacteria serve as pathogen‐associated molecular patterns (PAMPs) and could trigger specific inflammatory modulations. At the same time, phages could elicit innate antiviral immune responses. Toll‐like receptors (TLRs) operated as innate antiviral immune sensors and their activation triggers signaling cascades that lead to inflammatory response. J. Med. Virol. 88:1467–1472, 2016. © 2016 Wiley Periodicals, Inc.


"Fast, faster, and fastest: science on the run during COVID-19 drama"—"do not forget the liver"


title: Phosphorylation modulates liquid-liquid phase separation of the SARS-CoV-2 N protein

text: The nucleocapsid (N) protein of coronaviruses serves two major functions: compaction of the RNA genome in the virion and regulation of viral gene transcription in the infected cell1–3. The N protein contains two globular RNA-binding domains surrounded by regions of intrinsic disorder4. Phosphorylation of the central disordered region is required for normal viral genome transcription5,6, which occurs in a cytoplasmic structure called the replication transcription complex (RTC)7–11. It is not known how phosphorylation controls N protein function. Here we show that the N protein of SARS-CoV-2, together with viral RNA, forms biomolecular condensates12–15. Unmodified N protein forms partially ordered gel-like structures that depend on multivalent RNA-protein and protein-protein interactions. Phosphorylation reduces a subset of these interactions, generating a more liquid-like droplet. We speculate that distinct oligomeric states support the two functions of the N protein: unmodified protein forms a structured oligomer that is suited for nucleocapsid assembly, and phosphorylated protein forms a liquid-like compartment for viral genome processing. Inhibitors of N protein phosphorylation could therefore serve as antiviral therapy.


title: CD8 T cell responses to viral infections in sequence

text: Our current understanding of virus‐specific T cell responses has been shaped by model systems with mice, where naive animals are infected with a single viral pathogen. Paradigms derived from such models, however, may not always be applicable to a natural setting, where a host is exposed to numerous pathogens over its lifetime. Accumulating data in animal models and with some human diseases indicate that a host's prior history of infections can impact the specificity of future CD8 T cell responses, even to unrelated viruses. This can have both beneficial and detrimental consequences for the host, including altered clearance of virus, distinct forms of immunopathology, and substantial changes in the pool of memory T cells. Here we will describe the characteristics of CD8 T cells and the dynamics of their response to heterologous viral infections in sequence.


Rural Health Care Delivery Organizations and COVID‐19: Major Challenges and Implications for Health Care Management Education and Training


title: ''Tociluzumab challenge: A series of cytokine storm therapy experience in hospitalized Covid‐19 pneumonia patients''

text: OBJECTIVE: To recognize the period of exaggerated cytokine response in patients with Coronavirus disease 2019 (COVID‐19) pneumonia, and to describe the clinical outcomes of using tocilizumab as a treatment option. METHODS: The data of 12 adult COVID‐19 pneumonia patients who were followed in the inpatient clinics of Biruni University Medical Faculty Hospital (Istanbul, Turkey) were retrospectively analyzed. Diagnostic tests, laboratory examinations, clinical findings and computed tomography of the thorax imaging results were evaluated. RESULTS: A dramatic laboratory and clinical improvement was observed in 83% (10/12) of patients after tocilizumab. In 17% (2/12) of our patients, short‐term ventilator support was required in the intensive care unit. The longest hospital stay was 18 days. However, in the end, all of our patients were discharged home with health. While arterial oxygen saturations (87.58±3.12%) dropped in room air in the pre‐tocilizumab period, post‐tocilizumab they normalized in all patients (94.42±1%). None of them had fever after tocilizumab treatment and the levels of c‐reactive protein (13.08±12.89) were almost within normal limits. Eosinophil values were quite low at the time of diagnosis (10±17.06), but increased significantly post‐tocilizumab (155.33±192.69). CONCLUSION: There is currently no proven treatment for COVID‐19 induced by novel coronavirus SARS‐CoV‐2. Based on our experience with twelve adult COVID‐19 pneumonia patients, we can say that tocilizumab, an IL‐6 inhibitor, is more beneficial in preventing the damage caused by excessive cytokine response in the body if administered at the right time and provides clinical and radiological recovery. This article is protected by copyright. All rights reserved.


title: A relevance and quality-based ranking algorithm applied to evidence-based medicine

text: Abstract Background The amount of information available about millions of different subjects is growing every day. This has led to the birth of new search tools specialized in different domains, because classical information retrieval models have trouble dealing with the special characteristics of some of these domains. Evidence-based Medicine is a case of a complex domain where classical information retrieval models can help search engines retrieve documents by considering the presence or absence of terms, but these must be complemented with other specific strategies which allow retrieving and ranking documents including the best current evidence and methodological quality. Objective The goal is to present a ranking algorithm able to select the best documents for clinicians considering aspects related to the relevance and the quality of said documents. Methods In order to assess the effectiveness of this proposal, an experimental methodology has been followed by using Medline as a data set and the Cochrane Library as a gold standard. Results Applying the evaluation methodology proposed, and after submitting 40 queries on the platform developed, the MAP (Mean Average Precision) obtained was 20.26%. Conclusions Successful results have been achieved with the experiments, improving on other studies, but under different and even more complex circumstances.


Humanistic Epidemiology: Love in the time of cholera, COVID-19 and other outbreaks


La déontologie médicale à l’épreuve de l’épidémie de Covid 19: à propos de l’Hydroxychloroquine


title: Reprogrammed Pteropus Bat Stem Cells Present Distinct Immune Signature and are Highly Permissive for Henipaviruses

text: Bats are unique among mammals due to the ability of powered flight and exceptional longevity. They are also asymptomatic hosts for numerous viruses, including recently emerged zoonotic Henipaviruses Nipah and Hendra, which are highly pathogenic for humans and other mammals. Better understanding of how bats control viral infection requires development of relevant permissive cellular experimental models. By applying a somatic reprogramming protocol to Pteropus bat primary cells, using a novel combination of ESRRB, CDX2, and c-MYC transcription factors, we generated bat reprogrammed cells exhibiting stem cell-like characteristics and a neural stem cell-like molecular signature. These cells present a unique interferon-stimulated transcriptomic signature and both produce and respond to interferon type-I, highlighting differences between stem cells from bats and other mammals. In contrast to primary bat cells, these reprogrammed cells are highly susceptible to infection by Henipavirus, thereby enabling isolation of new bat viruses, study of virus-bat interactions, and better understanding of bat biology. Somatic reprogramming provides new bat stem cells with unique immune properties and original viral permissivness


title: Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design

text: Currently, there is limited knowledge about the immunological profiles of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) We used computer-based immunoinformatic analysis and the newly resolved 3-dimensional (3D) structures of the SARS-CoV-2 S trimeric protein, together with analyses of the immunogenic profiles of SARS-CoV, to anticipate potential B-cell and T-cell epitopes of the SARS-CoV-2 S protein for vaccine design, particularly for peptide-driven vaccine design and serological diagnosis Nine conserved linear B-cell epitopes and multiple discontinuous B-cell epitopes composed of 69 residues on the surface of the SARS-CoV-2 trimeric S protein were predicted to be highly antigenic We found that the SARS-CoV-2 S protein has a different antigenic profile than that of the SARS-CoV S protein due to the variations in their primary and 3D structures Importantly, SARS-CoV-2 may exploit an immune evasion mechanism through two point mutations in the critical and conserved linear neutralization epitope (overlap with fusion peptide) around a sparsely glycosylated area These mutations lead to a significant decrease in the antigenicity of this epitope in the SARS-CoV-2 S protein In addition, 62 T-cell epitopes in the SARS-CoV-2 S protein were predicted in our study The structure-based immunoinformatic analysis for the SARS-CoV-2 S protein in this study may improve vaccine design, diagnosis, and immunotherapy against the pandemic of COVID-19


title: Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection during late pregnancy: a report of 18 patients from Wuhan, China

text: BACKGROUND: Compared with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), Corona Virus Disease 2019(COVID-19) spread more rapidly and widely. The population was generally susceptible. However, reports on pregnant women infected with SARS-CoV-2 were very limited. By sharing the clinical characteristics, treatments and outcomes of 18 patients with COVID-19 during late pregnancy, we hope to provide some references for obstetric treatment and management. METHODS: A total of 18 patients with COVID-19 treated at Renmin Hospital of Wuhan University were collected. The epidemiological characteristics, clinical manifestations, laboratory tests, chest CT and pregnancy outcomes were performed for analysis. RESULTS: 1. 18 cases of late pregnancy infected with SARS-CoV-2 pneumonia were delivered at 35 (+ 5) weeks to 41 weeks. According to the clinical classification of COVID-19, 1 case was mild type, 16 cases were ordinary type, and 1 case was severe type. 2. According to imaging examinations: 15 (83%) cases showed unilateral or bilateral pneumonia, 2 (11%) cases had pulmonary infection with pleural effusion, and 1 (6%) case had no abnormal imaging changes. 8 (44%) cases were positive and 10 (56%) cases were negative for nasopharyngeal-swab tests of SARS-CoV-2. 3. Among the 18 newborns, there were 3 (17%) premature infants, 1 (6%) case of mild asphyxia, 5 (28%) cases of bacterial pneumonia, 1 (6%) case of gastrointestinal bleeding, 1 (6%) case of necrotizing enteritis, 2 (11%) cases of hyperbilirubinemia and 1 (6%) case of diarrhea. All the newborns were negative for the first throat swab test of SARS-CoV-2 after birth. 4. Follow-up to Mar 7, 2020, no maternal and neonatal deaths occurred. CONCLUSIONS: The majority of patients in late term pregnancy with COVID-19 were of ordinary type, and they were less likely to develop into critical pneumonia after early isolation and antiviral treatment. Vertical transmission of SARS-CoV-2 was not detected, but the proportion of neonatal bacterial pneumonia was higher than other neonatal diseases in newborns.


title: The respiratory virome and exacerbations in patients with chronic obstructive pulmonary disease

text: Introduction: Exacerbations are major contributors to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), and respiratory bacterial and viral infections are an important trigger for the occurrence of such exacerbations. However, using conventional diagnostic techniques, a causative agent is not always found. Metagenomic next-generation sequencing (mNGS) allows analysis of the complete virome, but has not yet been applied in COPD exacerbations. Objectives: To study the respiratory virome in nasopharyngeal samples during COPD exacerbations using mNGS. Study design: 88 nasopharyngeal swabs from 63 patients from the Bergen COPD Exacerbation Study (2006-2010) were analysed by mNGS and in-house qPCR for respiratory viruses. Both DNA and RNA were sequenced simultaneously using an Illumina library preparation protocol with in-house adaptations. Results: By mNGS, 23/88 samples tested positive. Sensitivity and specificity were both 96% for diagnostic targets (23/24 and 1067/1120, respectively). Viral pathogens only detected by mNGS were herpes simplex virus type 1 and coronavirus OC43. A positive correlation was found between Cq value and mNGS viral species reads (p=0.008). Patients with viral pathogens had lower percentages of bacteriophages (p<0.000). No correlation was found between viral reads (species and genus level) and clinical markers. Conclusions: The mNGS protocol used was highly sensitive and specific for semi-quantitative detection of respiratory viruses. Excellent negative predictive value implicates the power of mNGS to exclude any infectious cause in one test, with consequences for clinical decision making. Reduced abundance of bacteriophages in COPD patients with viral pathogens implicates skewing of the virome, and speculatively the bacterial population, during infection.


title: Induction of Antibodies Protecting against Transmissible Gastroenteritis Coronavirus (TGEV) by Recombinant Adenovirus Expressing TGEV Spike Protein

text: Abstract Ten recombinant adenoviruses expressing either fragments of 1135, 1587, or 3329 nt or the full-length spike gene of transmissible gastroenteritis coronavirus (TGEV) have been constructed. These recombinants produce S polypeptides with apparent molecular masses of 68, 86, 135, and 200 kDa, respectively. Expression of the recombinant antigen driven by Ad5 promoters was inhibited by the insertion of an exogenous SV-40 promoter. Most of the recombinant antigens remain intracytoplasmic in infected cells. All the recombinant-directed expression products contain functional antigenic sites C and B (Gebaueret al.,1991,Virology183, 225–238). The recombinant antigen of 135 kDa and that of 200 kDa, which represents the whole spike protein, also contain antigenic sites D and A, which have previously been shown to be the major inducers of TGEV-neutralizing antibodies. Interestingly, here we show that recombinant S protein fragments expressing only sites C and B also induced TGEV-neutralizing antibodies. The chimeric Ad5–TGEV recombinants elicited lactogenic immunity in hamsters, including the production of TGEV-neutralizing antibodies. The antisera induced in swine by the Ad5 recombinants expressing the amino-terminal 26% of the spike protein (containing sites C and B) or the full-length spike protein, when mixed with a lethal dose of virus prior to administration to susceptible piglets, delayed or completely prevented the induction of symptoms of disease, respectively.


docid: rydgncys

title: Willingness to accept a future influenza A(H7N9) vaccine in Beijing, China

text: Abstract Background The present study aimed to estimate residents’ willingness to accept a future H7N9 vaccine and its determinants in the general adult population in Beijing, China. Methods We conducted a multi-stage sampling, cross-sectional survey using self-administered anonymous questionnaires from May to June, in 2014. The main outcome variable was residents’ willingness to accept a future H7N9 vaccine. Logistic regression was used to identify the predictors of vaccination willingness. Results Of the 7264 eligible participants, 14.5% of Beijing residents reported that they had not heard of H7N9. Among those who had heard of H7N9, 59.5% of the general adult population would be willing to accept a future H7N9 vaccine, and approximately half of them reported ‘I am afraid of being infected by H7N9’ and ‘H7N9 vaccine can prevent infections’, and 28.1% reported ‘my daily life is affected by H7N9’. The variables that were significantly associated with a higher likelihood of reporting willingness were being younger adults (aged 18–29 years: OR = 1.52, 95% CI: 1.17–1.97; aged 30–39 years: OR = 1.39, 95% CI: 1.08–1.78), being farmers (OR = 1.61; 95% CI: 1.32–1.96), being unemployed people (OR = 1.36; 95% CI: 1.04–1.78), living in suburban areas (OR = 2.18; 95% CI: 1.89–2.51), having ≥2 children in the family (OR = 1.41; 95% CI: 1.03–1.92), perceived risk in China (OR = 1.30; 95% CI: 1.15–1.48), perceived susceptibility to disease (OR = 3.13; 95% CI: 2.73–3.58), perceived negative effect on daily life (OR = 1.32; 95% CI: 1.13–1.55), perceived effectiveness of vaccination (OR = 2.34; 95% CI: 2.07–2.64), and recent uptake of influenza vaccine (OR = 2.26; 95% CI: 1.92–2.66). Conclusions A great number of Beijing residents had doubts about the vaccine’s effectiveness and were not concerned about disease risk, which were the factors affecting willingness to be vaccinated. Targeted education programs on disease risk as well as vaccine’s effectiveness are needed to improve the willingness of vaccination for potential H7N9 pandemic preparedness.


title: Modeling mitigation of influenza epidemics by baloxavir

text: Influenza viruses annually kill 290,000–650,000 people worldwide. Antivirals can reduce death tolls. Baloxavir, the recently approved influenza antiviral, inhibits initiation of viral mRNA synthesis, whereas oseltamivir, an older drug, inhibits release of virus progeny. Baloxavir blocks virus replication more rapidly and completely than oseltamivir, reducing the duration of infectiousness. Hence, early baloxavir treatment may indirectly prevent transmission. Here, we estimate impacts of ramping up and accelerating baloxavir treatment on population-level incidence using a new model that links viral load dynamics from clinical trial data to between-host transmission. We estimate that ~22 million infections and >6,000 deaths would have been averted in the 2017–2018 epidemic season by administering baloxavir to 30% of infected cases within 48 h after symptom onset. Treatment within 24 h would almost double the impact. Consequently, scaling up early baloxavir treatment would substantially reduce influenza morbidity and mortality every year. The development of antivirals against the SARS-CoV2 virus that function like baloxavir might similarly curtail transmission and save lives.


title: A home hospitalization system based on the Internet of things, Fog computing and cloud computing

text: In recent years, the world has witnessed a significant increase in the number of elderly who often suffer from chronic diseases, and has witnessed in recent months a major spread of the new coronavirus (COVID-19), which has led to thousands of deaths, especially among the elderly and people who suffer from chronic diseases. Coronavirus has also caused many problems in hospitals, where these are no longer able to accommodate a large number of patients. This virus has also begun to spread between medical and paramedical teams, and this causes a major risk to the health of patients staying in hospitals. To reduce the spread of the virus and maintain the health of patients who need a hospital stay, home hospitalization is one of the best possible solutions. This paper proposes a home hospitalization system based on the Internet of Things (IoT), Fog computing, and Cloud computing, which are among the most important technologies that have contributed to the development of the healthcare sector in a significant way. These systems allow patients to recover and receive treatment in their homes and among their families, where patient health and the hospitalization room environmental state are monitored, to enable doctors to follow the hospitalization process and make recommendations to patients and their supervisors, through monitoring units and mobile applications developed for this purpose. The results of evaluation have shown great acceptance of this system by patients and doctors alike.


title: MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet

text: BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2−/− hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. METHODS: MuRF2−/− mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. RESULTS: MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2−/− hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2−/− hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2’s regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. CONCLUSIONS: Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARα and PPARγ1 activities in vivo via post-translational modification without degradation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0252-x) contains supplementary material, which is available to authorized users.


Investigations continue as SARS claims more lives


title: Yeast Based Small Molecule Screen for Inhibitors of SARS-CoV

text: Severe acute respiratory coronavirus (SARS-CoV) emerged in 2002, resulting in roughly 8000 cases worldwide and 10% mortality. The animal reservoirs for SARS-CoV precursors still exist and the likelihood of future outbreaks in the human population is high. The SARS-CoV papain-like protease (PLP) is an attractive target for pharmaceutical development because it is essential for virus replication and is conserved among human coronaviruses. A yeast-based assay was established for PLP activity that relies on the ability of PLP to induce a pronounced slow-growth phenotype when expressed in S. cerevisiae. Induction of the slow-growth phenotype was shown to take place over a 60-hour time course, providing the basis for conducting a screen for small molecules that restore growth by inhibiting the function of PLP. Five chemical suppressors of the slow-growth phenotype were identified from the 2000 member NIH Diversity Set library. One of these, NSC158362, potently inhibited SARS-CoV replication in cell culture without toxic effects on cells, and it specifically inhibited SARS-CoV replication but not influenza virus replication. The effect of NSC158362 on PLP protease, deubiquitinase and anti-interferon activities was investigated but the compound did not alter these activities. Another suppressor, NSC158011, demonstrated the ability to inhibit PLP protease activity in a cell-based assay. The identification of these inhibitors demonstrated a strong functional connection between the PLP-based yeast assay, the inhibitory compounds, and SARS-CoV biology. Furthermore the data with NSC158362 suggest a novel mechanism for inhibition of SARS-CoV replication that may involve an unknown activity of PLP, or alternatively a direct effect on a cellular target that modifies or bypasses PLP function in yeast and mammalian cells.


Recommendations for Physical Inactivity and Sedentary Behavior During the Coronavirus Disease (COVID-19) Pandemic