title: Discovery of novel low-molecular-weight HIV-1 inhibitors interacting with cyclophilin A using in silico screening and biological evaluations

text: Cyclophilin A has attracted attention recently as a new target of anti-human immunodeficiency virus type 1 (HIV-1) drugs. However, so far no drug against HIV-1 infection exhibiting this mechanism of action has been approved. To identify new potent candidates for inhibitors, we performed in silico screening of a commercial database of more than 1,300 drug-like compounds by using receptor-based docking studies. The candidates selected from docking studies were subsequently tested using biological assays to assess anti-HIV activities. As a result, two compounds were identified as the most active. Specifically, both exhibited anti-HIV activity against viral replication at a low concentration and relatively low cytotoxicity at the effective concentration inhibiting viral growth by 50 %. Further modification of these molecules may lead to the elucidation of potent inhibitors of HIV-1. [Figure: see text]


title: The Hepatitis C Virus-Induced Membranous Web in Liver Tissue

text: Host cell membrane rearrangements induced by the hepatitis C virus (HCV) have been exclusively studied in vitro. These studies have shown that HCV induces double-membrane vesicles (DMVs), which probably serve to separate replication sites from the cytoplasmic sensors of the innate immune response. We report for the first time the observation of HCV-induced membrane rearrangements in liver biopsy specimens from patients chronically infected with HCV. Unlike observations performed in vitro, the membranous web detected in liver tissue seems essentially made of clusters of single-membrane vesicles derived from the endoplasmic reticulum and close to lipid droplets. This suggests that the DMVs could be a hallmark of laboratory-adapted HCV strains, possibly due to their ability to achieve a high level of replication. Alternatively, the concealment of viral RNA in DMVs may be part of innate immune response mechanisms particularly developed in hepatoma cell lines cultured in vitro. In any case, this constitutes the first report showing the differences in the membranous web established by HCV in vitro and in vivo.


title: Early experience of COVID‐19 in 2 heart transplant recipients: Case reports and review of treatment options

text: The coronavirus disease 2019 (COVID‐19) pandemic poses special challenges to immunocompromised transplant patients. Given the paucity of proven data in treating COVID‐19, management of these patients is difficult, rapidly evolving, and mainly based on anecdotal experience. We report 2 cases of heart transplant (HT) recipients with COVID‐19. The first is a 59‐year‐old female with HT in 2012 who presented on March 20, 2020 with fever, hypoxia, and ground‐glass opacities on chest X‐ray. She quickly progressed to acute hypoxic respiratory failure and vasoplegic shock. Despite reduction in immunosuppression and treatment with tocilizumab, intravenous immunoglobulin, hydroxychloroquine, lopinavir/ritonavir, and broad‐spectrum antibiotics, she ultimately died from multiorgan failure. The second case is a 75‐year‐old man with HT in 2000 who presented on April 2, 2020 after curbside testing revealed positive COVID‐19. Given a milder presentation compared to the first patient, antimetabolite was discontinued and only hydroxychloroquine was started. Because of a lack of clinical improvement several days later, tocilizumab, methylprednisolone, and therapeutic anticoagulation were initiated. The patient clinically improved with decreasing oxygen requirements and was discharged home. These 2 cases highlight the wide range of different presentations of COVID‐19 in HT recipients and the rapidity with which the management of these patients is evolving.


title: Duties toward Patients with Psychiatric Illness

text: Patients with psychiatric illness feel the brunt of the intersection of many of our society's and our health care system's disparities, and the vulnerability of this population during the Covid‐19 pandemic cannot be overstated. Patients with psychiatric illness often suffer from the stigma of mental illness and receive poor medical care. Many patients with severe and persistent mental illness face additional barriers, including poverty, marginal housing, and food insecurity. Patients who require psychiatric hospitalization now face the risk of transmission of Covid‐19 due to the inherent difficulties of social distancing within a psychiatric hospital. Patients whose freedom and self‐determination have been temporarily overruled as they receive involuntary psychiatric treatment deserve a setting that maintains their health and safety. While tele‐mental health has been rapidly expanded to provide new ways to access psychiatric treatment, some patients may have limitations in technological literacy or access to devices. The social isolation, economic fallout, and potential traumatization related to the current pandemic will disproportionately affect this vulnerable population, and society's duties to them must be considered.


title: Comparison of pleural and esophageal pressure in supine and prone positions in a porcine model of acute respiratory distress syndrome

text: Patients with moderate to severe acute respiratory distress syndrome (ARDS) benefit from prone positioning. Although the accuracy of esophageal pressure (Pes) to estimate regional pleural pressure (Ppl) has previously been assessed in the supine position, such data are not available in the prone position in ARDS. In six anesthetized, paralyzed, and mechanically ventilated female pigs, we measured Pes and Ppl into dorsal and ventral parts of the right pleural cavity. Airway pressure (Paw) and flow were measured at the airway opening. Severe ARDS [arterial partial pressure of oxygen ([Formula: see text])/fraction of inspired oxygen ([Formula: see text]) < 100 mmHg at positive end-expiratory pressure (PEEP) of 5 cmH(2)O] was induced by surfactant depletion. In supine and prone positions assigned in a random order, PEEP was set to 20, 15, 10, and 5 cmH(2)O and static end-expiratory chest wall pressures were measured from Pes (PEEPtot,es) and dorsal (PEEPtot,PplD) and ventral (PEEPtot,PplV) Ppl. The magnitude of the difference between PEEPtot,es and PEEPtot,PplD was similar in each position [−3.6 cmH(2)O in supine vs. −3.8 cmH(2)O in prone at PEEP 20 cmH(2)O (PEEP 20)]. The difference between PEEPtot,es and PEEPtot,PplV became narrower in the prone position (−8.3 cmH(2)O supine vs. −3.0 cmH(2)O prone at PEEP 20). PEEPtot,PplV was overestimated by Pes in the prone position at higher pressures. The median (1st–3rd quartiles) dorsal-to-ventral Ppl gradient was 4.4 (2.4–6.8) cmH(2)O in the supine position and −1.5 (−3.5 to +1.1) cmH(2)O in the prone position (P < 0.0001) and marginally influenced by PEEP (P = 0.058). Prone position narrowed end-expiratory dorsal-to-ventral Ppl vertical gradient, likely because of a more even distribution of mechanical forces over the chest wall. NEW & NOTEWORTHY In a porcine model of acute respiratory distress syndrome, we found that static end-expiratory esophageal pressure did not change significantly in prone position compared with supine position at any positive end-expiratory pressure (PEEP) tested between 5 and 20 cmH(2)O. Prone position was associated with an increased ventral pleural pressure and reduced end-expiratory dorsal-to-ventral pleural pressure (Ppl) vertical gradient, likely due to a more even distribution of mechanical forces over the chest wall.


title: Jump point detection using empirical mode decomposition

text: Real estate is an important form of investment in Hong Kong. Recent researches on the analysis of real estate market have revealed that jump points in the housing price time series play an essential role in the Hong Kong economy. Detecting such jump points thus becomes important as they represent vital findings that enable policy-makers and investors to look forward. In this paper, we propose a jump point detection methodology, which makes use of the empirical mode decomposition algorithm and a derivative-based detector, to detect jump points in the time series of some housing price indices in Hong Kong. Experimental results reveal that our proposed method has a superior performance and outperforms the current state-of-the-art wavelet approach.


title: The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China

text: Abstract The pandemic outbreak of coronavirus disease 2019 (COVID-19) is rapidly spreading all over the world. Reports from China showed that about 20% of patients developed severe disease, resulting in a fatality of 4%. In the past two months, we clinical immunologists participated in multi-rounds of MDT (multidiscipline team) discussion on the anti-inflammation management of critical COVID-19 patients, with our colleagues dispatched from Chinese leading PUMC Hospital to Wuhan to admit and treat the most severe patients. Here, from the perspective of clinical immunologists, we will discuss the clinical and immunological characteristics of severe patients, and summarize the current evidence and share our experience in anti-inflammation treatment, including glucocorticoids, IL-6 antagonist, JAK inhibitors and choloroquine/hydrocholoroquine, of patients with severe COVID-19 that may have an impaired immune system.


title: Differential occupational risk for COVID‐19 and other infection exposure according to race and ethnicity

text: BACKGROUND: There are racial and ethnic disparities in the risk of contracting COVID‐19. This study sought to assess how occupational segregation according to race and ethnicity may contribute to the risk of COVID‐19. METHODS: Data about employment in 2019 by industry and occupation and race and ethnicity were obtained from the Bureau of Labor Statistics Current Population Survey. This data was combined with information about industries according to whether they were likely or possibly essential during the COVID‐19 pandemic and the frequency of exposure to infections and close proximity to others by occupation. The percentage of workers employed in essential industries and occupations with a high risk of infection and close proximity to others by race and ethnicity was calculated. RESULTS: People of color were more likely to be employed in essential industries and in occupations with more exposure to infections and close proximity to others. Black workers in particular faced an elevated risk for all of these factors. CONCLUSION: Occupational segregation into high‐risk industries and occupations likely contributes to differential risk with respect to COVID‐19. Providing adequate projection to workers may help to reduce these disparities.


title: The importance of cycle threshold values in interpreting molecular tests for SARS- CoV-2

text: Abstract Using the Allplex™ 2019-nCoV assay (Seegene, South Korea) 285 samples were tested, 49 (17%) were positive for 3 genes, four (1.4%) samples were positive for two genes (all N gene and RdRP gene), eight (3%) samples positive for one gene (all N gene only) and 224 (78.5%) samples were negative.


title: A molecular epidemiological perspective of rhinovirus types circulating in Amsterdam from 2007 to 2012

text: Abstract Rhinoviruses (RVs) are frequently detected respiratory viruses that cause mild common cold symptoms, but may also lead to more severe respiratory tract infections. The large number of RV types, classified into species A, B and C, hampers clear insights into the epidemiology and clinical significance of each RV type. The aim of this study was to map the circulation of RV types in the Amsterdam area. RV-positive nasopharyngeal and oropharyngeal samples, collected from 2007 to 2012 in the Academic Medical Centre (Amsterdam, the Netherlands), were typed based on the sequence of the region coding for capsid proteins VP4 and VP2. RV-A, RV-B and RV-C were found in proportions of of 52.4% (334/637), 11.3% (72/637), and 36.2% (231/637), respectively. We detected 129 of the 167 currently classified types. RVs circulated throughout the entire year with a peak in the autumn and a decline in the summer. Some RV types were observed throughout the entire sampling period and others had a more seasonal pattern. Nine RV-A and four RV-B novel provisionally assigned types were identified. This study provides an insight into the molecular epidemiology of RVs in the Amsterdam area. The RVs circulating are diverse and include several provisionally new types.


title: A Transmissible Gastroenteritis Coronavirus Nucleoprotein Epitope Elicits T Helper Cells That Collaborate in the in Vitro Antibody Synthesis to the Three Major Structural Viral Proteins

text: Abstract Four strong T cell epitopes have been identified studying the blastogenic response of lymphocytes from haplotype-defined transmissible gastroenteritis virus (TGEV) immune miniswine to sixty-one 15-mer synthetic peptides. Three of these epitopes are located on the nucleoprotein (N48 amino acids 46 to 60; N272, amino acids 272 to 286; and N321 amino acid 321 to 335), and one on the membrane protein (M196, amino acids 196 to 210). N321, peptide induced the highest T cell response and was recognized by immune miniswine lymphocytes with haplotypes dd, aa , and cc. T lymphocytes from peptide N321-immune miniswine reconstituted the in vitro synthesis of TGEV-specific antibodies by complementing CD4- TGEV-immune cells. This response was directed at least against the three major structural proteins. The synthesized antibodies specific for S protein preferentially recognized discontinous epitopes and neutralized TGEV infectivity. These results show that peptide N321 defines a functional T helper epitope eliciting T cells capable of collaborating with B cells specific for different proteins of TGEV.


title: Initial Clinical Impressions of the Critical Care of COVID-19 Patients in Seattle, New York City, and Chicago

text: Since the first recognition of a cluster of novel respiratory viral infections in China in late December 2019, intensivists in the United States have watched with growing concern as infections with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus―now named Coronavirus Disease of 2019 (COVID-19)―have spread to hospitals in the United States. Because COVID-19 is extremely transmissible and can progress to a severe form of respiratory failure, the potential to overwhelm available critical care resources is high and critical care management of COVID-19 patients has been thrust into the spotlight. COVID-19 arrived in the United States in January and, as anticipated, has dramatically increased the usage of critical care resources. Three of the hardest-hit cities have been Seattle, New York City, and Chicago with a combined total of over 14,000 cases as of March 23, 2020. In this special article, we describe initial clinical impressions of critical care of COVID-19 in these areas, with attention to clinical presentation, laboratory values, organ system effects, treatment strategies, and resource management. We highlight clinical observations that align with or differ from already published reports. These impressions represent only the early empiric experience of the authors and are not intended to serve as recommendations or guidelines for practice, but rather as a starting point for intensivists preparing to address COVID-19 when it arrives in their community.


title: Access to evidence‐based care for eating disorders during the COVID‐19 crisis

text: The COVID‐19 pandemic has forced an abrupt change in the delivery of clinical services, including for individuals with an eating disorder. We present this Virtual Issue as a resource for the eating disorder community to showcase research published in the International Journal of Eating Disorders that provides information on effective strategies to help address the challenges arising from COVID‐19‐related disruptions. Articles included describe original research or systematic reviews on obstacles to health services use and strategies to improve access to care; technological tools to provide or enhance interventions; patients' and clinicians' attitudes or perspectives on using digital tools for clinical care; factors influencing therapeutic alliance; and ideas for improving reach and uptake of digital interventions. We hope that readers will find ways to observe and record their own experiences during this global crisis; the experiences of people at risk for developing or exhibiting an eating disorder; and the experiences of those who care for people with an eating disorder. These lived experiences will be invaluable in formulating hypotheses for future studies in service of advancing the understanding of eating disorders and improving interventions and policies for reducing the burden of suffering attributable to eating disorders.


title: Brazilian oral medicine and oral pathology: we are here during the Covid‐19 pandemic

text: Coronavirus disease 19 (Covid‐19) was declared a pandemic by the World Health Organization on March 11(th), 2020 (https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen). As of May 19(th), 2020, approximately 4,731,458 cases of contamination and 316,169 deaths from Covid‐19 were recorded (https://who.sprinklr.com).


title: Puces à protéines et perspectives d’applications médicales

text: Résumé Les puces à protéines permettent de détecter les interactions moléculaires avec divers partenaires (protéines, peptides, acides nucléiques, sucres, etc.). Leurs avantages sont cruciaux pour l’analyse à haut débit des protéomes entiers de différents organismes. De plus, les résultats récents prouvent la performance des puces par rapport aux méthodes immunologiques conventionnelles. C’est pourquoi, les puces à antigènes et à anticorps deviennent des outils incontournables dans le domaine médical, en particulier, pour le diagnostic et le pronostic des maladies infectieuses, auto-immunes et allergiques. Les avancées technologiques permettent d’envisager l’introduction de puces miniaturisées dans la pratique médicale pour le monitoring multiparamétrique de pathologies humaines. Abstract Protein microarrays make it possible to detect molecular interactions with various partners (proteins, peptides, nucleic acids, sugars, etc.). Their advantages are crucial for high-throughput analysis of proteomes of different organisms. Moreover, the recent data reveal the performance of microarrays over current immunological methods. Therefore, the antigen and antibody microarrays become indispensable for medical applications, in particular, for diagnosis and prognosis of microbial infections, autoimmune and allergic diseases. The further technological progress might provide the extension of the miniaturized assays for multiparametric monitoring of human pathologies in practical medicine.


title: Diagnosis of Gallbladder Cancer Using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Profiling

text: Abstract: Proteomic fingerprint technology combining magnetic beads with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to profile and compare the serum proteins from 45 patients with gallbladder cancer and 50 healthy blood donors. The proteomic patterns were identified; the tree model of biomarkers was constructed and evaluated using the Biomarker Patterns Software. The model tree was constructed based on the 3 biomarkers (5913Da, 6181Da and 13,752Da), which generated excellent separation between the gallbladder cancer and control groups. The sensitivity was 86.7% and the specificity was 93.3%. The blind test data showed a sensitivity of 80% and a specificity of 90%. Taken together, our studies suggested that biomarkers for gallbladder cancer could be discovered in serum by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry combined with the use of magnetic beads. The pattern of combined markers would provide a powerful and reliable diagnostic method for gallbladder cancer with high sensitivity and specificity.


title: The role of penicillin in benign skin rashes in childhood: A prospective study based on drug rechallenge

text: Background Delayed-onset urticarial or maculopapular rashes are frequently observed in children treated with β-lactams. Many are labeled “allergic” without reliable testing. Objective Determine the etiology of these rashes by exploring both infectious and allergic causes. Methods Children presenting to the emergency department with delayed-onset urticarial or maculopapular rashes were enrolled. Acute and convalescent sera were obtained for viral screening along with a throat swab. Subjects underwent intradermal and patch skin testing for β-lactams 2 months after presentation. Anti–β-lactam blood allergy tests were also obtained. All subjects underwent an oral challenge test (OCT) with the culprit antibiotic. Results Eighty-eight children were enrolled between 2006 and 2008. There were 11 (12.5%) positive intradermal and no positive patch tests. There were 2 (2.3%) positive blood allergy tests. There were 6 (6.8%) subjects with a positive OCT, 2 were intradermal-negative, and 4 were intradermal-positive. No OCT reactions were more severe than the index event. Most subjects had at least 1 positive viral study, 54 (65.9%) in the OCT negative group. Conclusion In this situation, β-lactam allergy is clearly overdiagnosed because the skin rash is only rarely reproducible (6.8%) by a subsequent challenge. Viral infections may be an important factor in many of these rashes. OCTs were positive in a minority of intradermal skin test–positive subjects. Patch testing and blood allergy testing provided no useful information. OCTs should be considered in all children who develop a delayed-onset urticarial or maculopapular rash during treatment with a β-lactam.


title: Host-microbial interactions in patients with chronic rhinosinusitis

text: There has been considerable investigation of host-microbial interactions in patients with chronic rhinosinusitis (CRS) in hopes of elucidating mechanisms of disease and better treatment. Most attention has been paid to bacterial infection and potential underlying defects in innate immunity. Bacterial biofilm is present in most patients with CRS undergoing surgical intervention, and its presence is associated with more severe disease and worse surgical outcomes. A role for viral or fungal infection in patients with CRS is less clear. There is no evidence for a primary defect in mucociliary clearance in most patients with CRS. Decreased levels of certain antimicrobial proteins, most notably lactoferrin, have been found in sinus secretions, whereas levels of other antimicrobial proteins have been found to be normal. No primary defects in Toll-like receptors have been found in patients with CRS, although a 50% reduced expression of Toll-like receptor 9 was reported in patients with recalcitrant nasal polyps. A polymorphism in a bitter taste receptor was recently associated with refractory CRS and persistent Pseudomonas aeruginosa infection. A downregulation of innate immunity by maladaptive TH2 tissue inflammation has also been described in patients with recalcitrant nasal polyps, suggesting a link to persistent infection. To date, an effective means of restoring host-microbial balance and mitigating disease in patients with CRS remains elusive.


title: Molecular Screening by Polymerase Chain Reaction Detects Panleukopenia Virus DNA in Formalin-Fixed Hearts from Cats with Idiopathic Cardiomyopathy and Myocarditis

text: Abstract Viral myocarditis has been suggested as an etiology for cardiomyopathy in several mammalian species. Myocarditis and idiopathic cardiomyopathy have been reported in the domestic cat, although a viral etiology has not been demonstrated. Because of the continuing interest in the potential relationship between viral myocarditis and cardiomyopathy, we evaluated hearts from cats with spontaneous, idiopathic cardiomyopathy for viral genomic material within myocytes by polymerase chain reaction, and for the presence of myocarditis by light microscopy. Thirty-one (31) formalin-fixed hearts from domestic cats who died of idiopathic cardiomyopathy were randomly selected from pathology archives. Seventeen (17) formalin-fixed hearts from healthy cats were similarly selected as normal controls. The polymerase chain reaction (PCR) was used to evaluate myocardial tissue for the presence of viral genome from feline panleukopenia virus, herpes virus, calici virus, and corona virus. Hearts were examined using light microscopy for histologic evidence of myocarditis according to the Dallas criteria. Panleukopenia virus was identified by PCR in 10 of 31 cats with cardiomyopathy but in none of the controls. Neither cardiomyopathic or control cats tested positive by PCR for herpes virus, calici virus, and corona virus. Myocarditis was detected by histologic examination in 18 of 31 cardiomyopathic cats and in none of 17 control cats. Myocarditis and or feline panleukopenia virus genome was detected in felines with idiopathic hypertrophic, dilated, and restrictive cardiomyopathy, suggesting a possible role of viral infection and inflammation in the pathogenesis of cardiomyopathy in this species.


title: A single bat species in Cameroon harbors multiple highly divergent papillomaviruses in stool identified by metagenomics analysis

text: Abstract A number of PVs have been described in bats but to the best of our knowledge not from feces. Using a previously described NetoVIR protocol, Eidolon helvum pooled fecal samples (Eh) were treated and sequenced by Illumina next generation sequencing technology. Two complete genomes of novel PVs (EhPV2 and EhPV3) and 3 partial sequences (BATPV61, BATPV890a and BATPV890b) were obtained and analysis showed that the EhPV2 and EhPV3 major capsid proteins cluster with and share 60–64% nucleotide identity with that of Rousettus aegyptiacus PV1, thus representing new species of PVs within the genus Psipapillomavirus. The other PVs clustered in different branches of our phylogenetic tree and may potentially represent novel species and/or genera. This points to the vast diversity of PVs in bats and in Eidolon helvum bats in particular, therefore adding support to the current concept that PV evolution is more complex than merely strict PV-host co-evolution.


title: Data on the stability of darunavir/cobicistat suspension after tablet manipulation

text: Abstract The COVID-19 outbreak is now one of the most critical crises to manage for most of the national healthcare systems in the world. In the absence of authorised pharmacological treatments, many antiretrovirals, including darunavir/cobicistat fixed combination, were used off-label in the hospital wards as life-treating medicines for COVID-19 patients. Unfortunately, for most of them, the drug products available on the market are not designed to be administered by a nasogastric tube to inpatients of intensive care units. Therefore, their manipulation, even if it can strongly affect the product quality, is necessary for the preparation of suspension to meet patients’ need. In this situation, it is urgent to provide data and guidance to support hospital pharmacist and clinicians in their activity. The data in this article indicate that darunavir/cobicistat suspensions compounded by pharmacists using as active ingredient a commercially available tablet can be stable at least for one week.


title: Interferon gamma inhibits transmissible gastroenteritis virus infection mediated by an IRF1 signaling pathway

text: Interferon gamma (IFN-γ) is best known for its ability to regulate host immune responses; however, its direct antiviral activity is less well studied. Transmissible gastroenteritis virus (TGEV) is an economically important swine enteric coronavirus and causes acute diarrhea in piglets. At present, little is known about the function of IFN-γ in the control of TGEV infection. In this study, we demonstrated that IFN-γ inhibited TGEV infection directly in ST cells and intestine epithelial IPEC-J2 cells and that the anti-TGEV activity of IFN-γ was independent of IFN-α/β. Moreover, IFN-γ suppressed TGEV infection in ST cells more efficiently than did IFN-α, and the combination of IFN-γ and IFN-α displayed a synergistic effect against TGEV. Mechanistically, using overexpression and functional knockdown experiments, we demonstrated that porcine interferon regulatory factor 1 (poIRF1) elicited by IFN-γ primarily mediated IFN-γ signaling cascades and the inhibition of TGEV infection by IFN-γ. Importantly, we found that TGEV elevated the expression of poIRF1 and IFN-γ in infected small intestines and peripheral blood mononuclear cells. Thus, IFN-γ plays a crucial role in curtailing enteric coronavirus infection and may serve as an effective prophylactic and/or therapeutic agent against TGEV infection.


title: Phenotypic alterations and survival of monocytes following infection by human herpesvirus-6

text: Freshly isolated monocytes rapidly undergo physiological changes in vitro, resulting in programmed cell death (apoptosis). Activation of monocytes, which promotes differentiation into macrophages, is known to inhibit apoptotic processes. In the present study, we report that human herpesvirus-6 (HHV-6) prevents monocytes from undergoing spontaneous apoptosis during the first 72 hours of culture. Furthermore, significant alterations in cell-surface phenotype were observed after 72 hours of infection with HHV-6. HHV-6-infected monocyte cultures have considerably reduced levels of CD14, CD64 (FcγRI) and HLA-DR antigen on their surface, while CD32 (FcγRII) expression is unaffected. On the basis of these results, we hypothesize that HHV-6 promotes monocytes survival and causes phenotypic modifications that could favor immune evasion and ensure its persistence within the infected host.


docid: emoexjwq

title: Rapid detection of porcine parvovirus DNA by sensitive loop-mediated isothermal amplification

text: Abstract A method of loop-mediated isothermal amplification (LAMP) was employed to develop a rapid and simple detection system for porcine parvovirus (PPV) DNA. The amplification could be finished in 45min under isothermal condition at 62°C by employing a set of four primers targeting VP2 gene of PPV. LAMP assay showed higher sensitivity than PCR, with a detection limit of 5 copies of PPV genomic DNA per reaction. No cross reactivity was observed from the samples of other related viruses including canine parvovirus, parvovirus B19, porcine circovirus type 1, porcine circovirus type 2 and porcine peudorabies virus. The detection rate of PPV LAMP for 125 clinical samples was 97.6% and appeared higher than that of PCR method. The result indicated the potential usefulness of the technique as a simple, rapid procedure for the detection of PPV.


Why not consider an endothelin receptor antagonist against SARS‐CoV‐2?


title: Modelling the downhill of the Sars-Cov-2 in Italy and a universal forecast of the epidemic in the world

text: In a previous article [1] we have described the temporal evolution of the Sars-Cov-2 in Italy in the time window February 24-April 1. As we can see in [1] a generalized logistic equation captures both the peaks of the total infected and the deaths. In this article our goal is to study the missing peak, i.e. the currently infected one (or total currently positive). After the April 7 the large increase in the number of swabs meant that the logistical behavior of the infected curve no longer worked. So we decided to generalize the model, introducing new parameters. Moreover, we adopt a similar approach used in [1] (for the estimation of deaths) in order to evaluate the recoveries. In this way, introducing a simple conservation law, we define a model with 4 populations: total infected, currently positives, recoveries and deaths. Therefore, we propose an alternative method to a classical SIRD model for the evaluation of the Sars-Cov-2 epidemic. However, the method is general and thus applicable to other diseases. Finally we study the behavior of the ratio infected over swabs for Italy, Germany and USA, and we show as studying this parameter we recover the generalized Logistic model used in [1] for these three countries. We think that this trend could be useful for a future epidemic of this coronavirus.


docid: tsmnkuhw

title: Pathology of US Porcine Epidemic Diarrhea Virus Strain PC21A in Gnotobiotic Pigs

text: To understand the progression of porcine epidemic diarrhea virus infection, we inoculated gnotobiotic pigs with a newly emerged US strain, PC21A, of the virus. At 24–48 hours postinoculation, the pigs exhibited severe diarrhea and vomiting, fecal shedding, viremia, and severe atrophic enteritis. These findings confirm that strain PC21A is highly enteropathogenic.


title: Bacterial Pneumonia in Older Adults

text: The incidence of pneumonia increases with age, and is particularly high in patients who reside in long-term care facilities (LTCFs). Mortality rates for pneumonia in older adults are high and have not decreased in the last decade. Atypical symptoms and exacerbation of underlying illnesses should trigger clinical suspicion of pneumonia. Risk factors for multidrug-resistant organisms are more common in older adults, particularly among LTCF residents, and should be considered when making empiric treatment decisions. Monitoring of clinical stability and underlying comorbid conditions, potential drug–drug interactions, and drug-related adverse events are important factors in managing elderly patients with pneumonia.


docid: jkyltjap

title: Locally Informed Simulation to Predict Hospital Capacity Needs During the COVID-19 Pandemic

text: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic challenges hospital leaders to make time-sensitive, critical decisions about clinical operations and resource allocations. OBJECTIVE: To estimate the timing of surges in clinical demand and the best- and worst-case scenarios of local COVID-19–induced strain on hospital capacity, and thus inform clinical operations and staffing demands and identify when hospital capacity would be saturated. DESIGN: Monte Carlo simulation instantiation of a susceptible, infected, removed (SIR) model with a 1-day cycle. SETTING: 3 hospitals in an academic health system. PATIENTS: All people living in the greater Philadelphia region. MEASUREMENTS: The COVID-19 Hospital Impact Model (CHIME) (http://penn-chime.phl.io) SIR model was used to estimate the time from 23 March 2020 until hospital capacity would probably be exceeded, and the intensity of the surge, including for intensive care unit (ICU) beds and ventilators. RESULTS: Using patients with COVID-19 alone, CHIME estimated that it would be 31 to 53 days before demand exceeds existing hospital capacity. In best- and worst-case scenarios of surges in the number of patients with COVID-19, the needed total capacity for hospital beds would reach 3131 to 12 650 across the 3 hospitals, including 338 to 1608 ICU beds and 118 to 599 ventilators. LIMITATIONS: Model parameters were taken directly or derived from published data across heterogeneous populations and practice environments and from the health system's historical data. CHIME does not incorporate more transition states to model infection severity, social networks to model transmission dynamics, or geographic information to account for spatial patterns of human interaction. CONCLUSION: Publicly available and designed for hospital operations leaders, this modeling tool can inform preparations for capacity strain during the early days of a pandemic. PRIMARY FUNDING SOURCE: University of Pennsylvania Health System and the Palliative and Advanced Illness Research Center.


title: Chapter Two Fly foregut and transmission of microbes

text: Abstract Two areas of research that have greatly increased in attention are: dipterans as vectors and the microbes they are capable of vectoring. Because it is the front-end of the fly that first encounters these microbes, this review focuses on the legs, mouthparts, and foregut, which includes the crop as major structures involved in dipteran vectoring ability. The legs and mouthparts are generally involved in mechanical transmission of microbes. However, the crop is involved in more than just mechanical transmission, for it is within the lumen of the crop that microbes are taken up with the meal of the fly, stored, and it is within the lumen that horizontal transmission of bacterial resistance has been demonstrated. In addition to storage of microbes, the crop is also involved in depositing the microbes via a process known as regurgitation. Various aspects of crop regulation are discussed and specific examples of crop involvement with microorganisms are discussed. The importance of biofilm and biofilm formation are presented, as well as, some physical parameters of the crop that might either facilitate or inhibit biofilm formation. Finally, there is a brief discussion of dipteran model systems for studying crop microbe interactions.


title: Disparities in Vulnerability to Severe Complications from COVID-19 in the United States

text: This paper provides the first nationally representative estimates of vulnerability to severe complications from COVID-19 overall and across race-ethnicity and socioeconomic status. We use the Panel Study of Income Dynamics (PSID) to examine the prevalence of specific health conditions associated with complications from COVID-19 and to calculate, for each individual, an index of the risk of severe complications from respiratory infections developed by DeCaprio et al. (2020). We show large disparities across race-ethnicity and socioeconomic status in the prevalence of conditions, including hypertension, which are associated with the risk of severe complications from COVID-19. Moreover, we show that these disparities emerge early in life, prior to age 65, leading to higher vulnerability to such complications. Our results suggest particular attention should be paid to the risk of adverse outcomes in midlife for non-Hispanic blacks, adults with a high school degree or less, and low-income Americans.


title: Imported Case of Acute Respiratory Tract Infection Associated with a Member of Species Nelson Bay Orthoreovirus

text: A Japanese man suffered from acute respiratory tract infection after returning to Japan from Bali, Indonesia in 2007. Miyazaki-Bali/2007, a strain of the species of Nelson Bay orthoreovirus, was isolated from the patient's throat swab using Vero cells, in which syncytium formation was observed. This is the sixth report describing a patient with respiratory tract infection caused by an orthoreovirus classified to the species of Nelson Bay orthoreovirus. Given the possibility that all of the patients were infected in Malaysia and Indonesia, prospective surveillance on orthoreovirus infections should be carried out in Southeast Asia. Furthermore, contact surveillance study suggests that the risk of human-to-human infection of the species of Nelson Bay orthoreovirus would seem to be low.


title: Bridging the gap between education and practice in public health, with particular reference to less-developed provinces in China

text: Summary Ongoing healthcare system reform is one of the most important issues in China. There is an increasing awareness that public health education should be reformed to meet the demands of public health practice. This paper summarizes the current status of increasing public healthcare demand and public health service capacity in China, especially in less-developed provinces, and introduces the current public health educational system and public health administration structure. The paper also provides evidence for a considerable gap between public health education and practice, and suggests possible measures to bridge the gap.


title: Recombinant measles viruses expressing single or multiple antigens of human immunodeficiency virus (HIV-1) induce cellular and humoral immune responses

text: Recombinant measles viruses (rMV) based on the live attenuated measles vaccine strain (MVb) expressing antigens of HIV-1 clade B were generated by reverse genetics. Recombinants expressing single or double antigens of HIV-1 (rMV-HIV) were genetically highly stable on human diploid cells. The production process of these viruses was essentially similar to the parental MV strain, yielding comparative end titers. Immunization of tg-mice by different regimens and formulations showed potent humoral and cellular immune responses against MV and HIV antigens. Recombinant MV-HIV expressing Gag protein conferred protective immunity in tg-mice after a high-dose pseudochallenge with recombinant vaccinia virus. In addition, rMV-HIV boosted anti-HIV antibodies, in the presence of pre-existing anti-vector antibodies.


title: Regulating the adaptive immune response to respiratory virus infection

text: Recent years have seen several advances in our understanding of immunity to virus infection of the lower respiratory tract, including to influenza virus infection. Here, we review the cellular targets of viruses and the features of the host immune response that are unique to the lungs. We describe the interplay between innate and adaptive immune cells in the induction, expression and control of antiviral immunity, and discuss the impact of the infected lung milieu on moulding the response of antiviral effector T cells. Recent findings on the mechanisms that underlie the increased frequency of severe pulmonary bacterial infections following respiratory virus infection are also discussed.


title: Inhibition of arterivirus RNA synthesis by cyclophilin inhibitors is counteracted by mutations in replicase transmembrane subunits

text: Previously, the cyclophilin inhibitors cyclosporin A (CsA) and Alisporivir (ALV) were shown to inhibit the replication of diverse RNA viruses, including arteriviruses and coronaviruses, which both belong to the order Nidovirales. Here we aimed to identify arterivirus proteins involved in the mode-of-action of cyclophilin inhibitors and to investigate how these compounds inhibit arterivirus RNA synthesis in the infected cell. Repeated passaging of the arterivirus prototype equine arteritis virus (EAV) in the presence of CsA revealed that reduced drug sensitivity is associated with the emergence of adaptive mutations in nonstructural protein 5 (nsp5), one of the transmembrane subunits of the arterivirus replicase polyprotein. Introduction of singular nsp5 mutations (nsp5 Q21R, Y113H, or A134V) led to a ∼2-fold decrease in sensitivity to CsA treatment, whereas combinations of mutations further increased EAV’s CsA resistance. The detailed experimental characterization of engineered EAV mutants harboring CsA-resistance mutations implicated nsp5 in arterivirus RNA synthesis. Particularly, in an in vitro assay, EAV RNA synthesis was far less sensitive to CsA treatment when nsp5 contained the adaptive mutations mentioned above. Interestingly, for increased sensitivity to the closely-related drug ALV CsA-resistant nsp5 mutants required the incorporation of an additional adaptive mutation, which resided in nsp2 (H114R), another transmembrane subunit of the arterivirus replicase. Our study provides the first evidence for the involvement of nsp2 and nsp5 in the mechanism underlying the inhibition of arterivirus replication by cyclophilin inhibitors. Importance Currently, no approved treatments are available to combat infections with nidoviruses, a group of plus-stranded RNA viruses including important zoonotic and veterinary pathogens. Previously, the cyclophilin inhibitors cyclosporin A (CsA) and Alisporivir (ALV) were shown to inhibit the replication of diverse nidoviruses (both arteriviruses and coronaviruses), and may thus represent a class of pan-nidovirus inhibitors. Here, using the arterivirus prototype equine arteritis virus, we have established that resistance to CsA and ALV treatment is associated with adaptive mutations in two trans-membrane subunits of the viral replication complex, nonstructural proteins 2 and 5. This is the first evidence for the involvement of specific replicase subunits of nidoviruses in the mechanism underlying the inhibition of their replication by cyclophilin inhibitors. Understanding this mechanism of action is of major importance to guide future drug design, both for nidoviruses and other RNA viruses inhibited by these compounds.


title: COVID-19 in health-care workers in three hospitals in the south of the Netherlands: a cross-sectional study

text: BACKGROUND: 10 days after the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Netherlands (on Feb 27, 2020), 55 (4%) of 1497 health-care workers in nine hospitals located in the south of the Netherlands had tested positive for SARS-CoV-2 RNA. We aimed to gain insight in possible sources of infection in health-care workers. METHODS: We did a cross-sectional study at three of the nine hospitals located in the south of the Netherlands. We screened health-care workers at the participating hospitals for SARS-CoV-2 infection, based on clinical symptoms (fever or mild respiratory symptoms) in the 10 days before screening. We obtained epidemiological data through structured interviews with health-care workers and combined this information with data from whole-genome sequencing of SARS-CoV-2 in clinical samples taken from health-care workers and patients. We did an in-depth analysis of sources and modes of transmission of SARS-CoV-2 in health-care workers and patients. FINDINGS: Between March 2 and March 12, 2020, 1796 (15%) of 12 022 health-care workers were screened, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete and near-complete genome sequences from 50 health-care workers and ten patients. Most sequences were grouped in three clusters, with two clusters showing local circulation within the region. The noted patterns were consistent with multiple introductions into the hospitals through community-acquired infections and local amplification in the community. INTERPRETATION: Although direct transmission in the hospitals cannot be ruled out, our data do not support widespread nosocomial transmission as the source of infection in patients or health-care workers. FUNDING: EU Horizon 2020 (RECoVer, VEO, and the European Joint Programme One Health METASTAVA), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health.


title: Understanding the age divide in COVID-19: why are children overwhelmingly spared?

text: The rapid emergence and subsequent global dissemination of SARS-CoV-2 disease (COVID-19) has resulted in over 4 million cases worldwide. The disease has a marked predilection for adults, and children are relatively spared. Understanding the age-based differences in pathophysiological pathways and processes relevant to the onset and progression of disease both in the clinical course and in experimental disease models may hold the key to the identification of therapeutic targets. The differences in the clinical course are highlighted by the lack of progression of the SARS-CoV-2 infection beyond mild symptoms in a majority of children, whereas in adults the disease progresses to acute lung injury and an acute respiratory distress syndrome (ARDS)-like phenotype with high mortality. The pathophysiological mechanisms leading to decreased lung injury in children may involve the decreased expression of the mediators necessary for viral entry into the respiratory epithelium and differences in the immune system responses in children. Specifically, decreased expression of proteins, including angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) in the airway epithelium in children may prevent viral entry. The immune system differences may include a relative preponderance of CD4(+) T cells, decreased neutrophil infiltration, decreased production of proinflammatory cytokines, and increased production of immunomodulatory cytokines in children compared with adults. Notably, the developing lung in children may have a greater capacity to recover and repair after viral infection. Understanding the relative contributions of the above processes to the protective phenotype in the developing lung can guide the trial of the appropriate therapies in adults.


Emergency changes in International Guidelines on Treatment for Head and Neck Cancer Patients During the COVID-19 Pandemic


title: Instructor-based Real-time Multimedia Medical Simulation to Update Concepts of Difficult Airway Management for Experienced Airway Practitioners

text: Background We integrated lecture, real-time multimedia display and medical simulation into a new renewal airway management training protocol for experienced nurse anesthetists. Methods Trainees of the Taiwan Association of Nurse Anesthetists from northern Taiwan and junior residents from our department were enrolled into the training program. A 4-hour renewal curriculum in the management of airway emergen-cies was developed, which consisted of a 2-hour general lecture (including 4 divided sections) and a 2-hour instructor-based real-time multimedia medical simulation of 4 specific techniques. After detailed explanation of each specific instrument at the beginning of each simulation, the instructors demonstrated accurate and successful management of 4 airway crises from clinical experience by using a standardized human patient simulator situated on the stage of the conference room. Meanwhile, real-time display of instructors’ performance, responsive physical parameters and images from specific instruments were conducted by video camera and video processor, and projected on a 3-frame screen. Brief summary and feedback were performed after each simulation. Trainees completed a questionnaire 6 months after they participated in the training program. Results Two hundred and forty-two nurse anesthetists and 13 young residents were trained with this protocol. The questionnaire revealed that the renewal training program was useful. Participants updated their knowledge of difficult airway management, gained more confidence, improved performance, and provided effective assistance in handling airway crises. Conclusion Renewing practice guidelines and teaching airway management skills, especially for difficult airway crises and protection of personnel, continues to be an important issue. Instructor-based real-time multimedia simulation is a fast, useful and systematic renewal educational method for many participants with extensive experience of airway management to update their knowledge about difficult airway management, and acquire improved decision-making and communication capabilities, skills of specific airway management. [J Chin Med Assoc 2008;71(4):174–179]


docid: xqsvical

title: News on patent, trade mark and design databases on the internet

text: • Patent offices launch COVID-19 information collections. • Design image similarity search from Japan. • New user interface for TMView and DesignView.


title: COVID-19 no município do Rio de Janeiro: análise espacial da ocorrência dos primeiros casos e óbitos confirmados/ COVID-19 en la ciudad de Rio de Janeiro: análisis espacial de la ocurrencia de los primeros casos y muertes confirmadas/ COVID-19 in the city of Rio de Janeiro: spatial analysis of first confirmed cases and deaths

text: Resumo Objetivo descrever a distribuição espacial dos primeiros casos e óbitos confirmados de COVID-19 do Rio de Janeiro. Métodos estudo ecológico de casos e óbitos confirmados de SARS-CoV-2 entre 6 de março e 10 de abril de 2020. Calcularam-se as taxas de incidência, taxas de mortalidade, letalidade, excesso de risco e índices global e local de Moran. Resultados foram registrados 1.808 casos e 92 óbitos confirmados. A taxa de incidência de COVID-19 foi 26,8/100 mil hab., a taxa de mortalidade, 1,36/100 mil hab., e a letalidade, 5%. Oito bairros exibiram taxa de incidência de 4 a 12 vezes superior à do município: Joá, na Zona Oeste; Cosme Velho, Gávea, Ipanema, Jardim Botânico, Lagoa, Leblon e São Conrado, na Zona Sul. Conclusão observou-se alto risco de infecção e morte por COVID-19 em bairros da Zona Sul do município do Rio de Janeiro; bairros da Zona Norte também se destacam em relação ao alto risco de morte.(AU)


title: Characteristics and prognostic factors of disease severity in patients with COVID-19: The Beijing experience

text: Abstract COVID-19 has become one of the worst infectious disease outbreaks of recent times, with over 2.1 million cases and 120,000 deaths so far. Our study investigated the demographic, clinical, laboratory and imaging features of 63 patients with COVID-19 in Beijing. Patients were classified into four groups, mild, moderate, severe and critically ill. The mean age of our patients was 47 years of age (range 3–85) and there was a slight male predominance (58.7%). Thirty percent of our patients had severe or critically ill disease, but only 20% of severe and 33% of critically ill patients had been to Wuhan. Fever was the most common presentation (84.1%), but cough was present in only slightly over half of the patients. We found that lymphocyte and eosinophils count were significantly decreased in patients with severe disease (p = 0.001 and p = 0.000, respectively). Eosinopenia was a feature of higher levels of severity. Peripheral CD4+, CD8+ T lymphocytes, and B lymphocytes were significantly decreased in severe and critically ill patients, but there was only a non-statistically significant downward trend in NK cell numbers with severity. Of note is that liver function test including AST, ALT, GGT and LDH were elevated, and albumin was decreased. The inflammatory markers CRP, ESR and ferritin were elevated in patients with severe disease or worse. IL-6 levels were also higher, indicating that the presence of a hyperimmune inflammatory state portends higher morbidity and mortality. In a binary logistic regression model, C-reactive protein level (OR 1.073, [CI, 1.013–1.136]; p = 0.017), CD8 T lymphocyte counts (OR 0.989, [CI, 0.979–1.000]; p = 0.043), and D-dimer (OR 5.313, [CI, 0.325–86.816]; p = 0.241) were independent predictors of disease severity.


title: Health services provision of 48 public tertiary dental hospitals during the COVID-19 epidemic in China

text: OBJECTIVES: To assess the status of health services provision of public tertiary dental hospitals during the COVID-19 epidemic in China and to evaluate the regional difference of telehealth. MATERIALS AND METHODS: The health services provision of public tertiary dental hospitals in China mainland during the COVID-19 epidemic was inquired. The status of non-emergency dental services, emergency dental services, and online professional consultation and the hospitals’ geographical distribution were recorded and analyzed. RESULTS: All the 48 public tertiary dental hospitals suspended general non-emergency dental treatment while providing emergency dental services only. Ninety percent of them notified the change of dental services online, and 69% of them offered free online professional consultations. The penetration rate of online technology was significantly higher in the eastern region than that of the central and western regions. CONCLUSIONS: There was a significant change in the health service provision of Chinese public tertiary dental hospitals during the COVID-19 epidemic and wider use of telehealth in the eastern region. CLINICAL RELEVANCE: This report demonstrated that dental health services were significantly affected by the COVID-19 epidemic in China, which might lead to a long-time impact on dental care in the future.


title: Inactivation and stability of viral diagnostic reagents treated by gamma radiation

text: Abstract The objective of this study was to apply the pertinent findings from gamma inactivation of virus infectivity to the production of high quality diagnostic reagents. A Gammacell 220 (Atomic Energy of Canada, Ltd., Ottawa, Canada § § Use of trade names is for identification only and does not imply endorsement by the Public Health Service or by the U.S. Department of Health and Human Services. ) was used to subject 38 viruses grown in either susceptible tissue cultures or embryonated chicken eggs to various doses of gamma radiation from a cobalt-60 source. The radiation required to reduce viral infectivity was 0·42 to 3·7 megarads (Mrad). The effect of gamma treatment on the antigenic reactivity of reagents for the complement fixation (CF), hemagglutination (HA) and neuraminadase assays was determined. Influenza antigens inactivated with 1·7 Mrad displayed comparable potency, sensitivity, specificity and stability to those inactivated by standard procedures with beta-propiolactone (BPL). Significant inactivation of influenza N1 and B neuraminidase occurred with >2·4 Mrad radiation at temperatures above 4°C. All 38 viruses were inactivated, and CF or HA antigens were prepared successfully. Antigenic potency remained stable with all antigens for 3 years and with 83% after 5 years storage. Influenza HA antigens evaluated after 9 years of storage demonstrated 86% stability. Gamma radiation is safer than chemical inactivation procedures and is a reliable and effective replacement for BPL in preparing diagnostic reagents.


title: Chloroquine Dosing Recommendations for Pediatric COVID‐19 Supported by Modeling and Simulation

text: As chloroquine (CHQ) is part of the Dutch Centre for Infectious Disease Control coronavirus disease 2019 (COVID‐19) experimental treatment guideline, pediatric dosing guidelines are needed. Recent pediatric data suggest that existing World Health Organization (WHO) dosing guidelines for children with malaria are suboptimal. The aim of our study was to establish best‐evidence to inform pediatric CHQ doses for children infected with COVID‐19. A previously developed physiologically‐based pharmacokinetic (PBPK) model for CHQ was used to simulate exposure in adults and children and verified against published pharmacokinetic data. The COVID‐19 recommended adult dosage regimen of 44 mg/kg total was tested in adults and children to evaluate the extent of variation in exposure. Based on differences in area under the concentration‐time curve from zero to 70 hours (AUC(0–70h)) the optimal CHQ dose was determined in children of different ages compared with adults. Revised doses were re‐introduced into the model to verify that overall CHQ exposure in each age band was within 5% of the predicted adult value. Simulations showed differences in drug exposure in children of different ages and adults when the same body‐weight based dose is given. As such, we propose the following total cumulative doses: 35 mg/kg (CHQ base) for children 0–1 month, 47 mg/kg for 1–6 months, 55 mg/kg for 6 months–12 years, and 44 mg/kg for adolescents and adults, not to exceed 3,300 mg in any patient. Our study supports age‐adjusted CHQ dosing in children with COVID‐19 in order to avoid suboptimal or toxic doses. The knowledge‐driven, model‐informed dose selection paradigm can serve as a science‐based alternative to recommend pediatric dosing when pediatric clinical trial data is absent.


docid: iaiosjlu

title: Mask use during COVID-19: A risk adjusted strategy()

text: In the context of Coronavirus Disease (2019) (COVID-19) cases globally, there is a lack of consensus across cultures on whether wearing face masks is an effective physical intervention against disease transmission. This study 1) illustrates transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); 2) addresses controversies surrounding the mask from perspectives of attitude, effectiveness, and necessity of wearing the mask with evidence that the use of mask would effectively interrupt the transmission of infectious diseases in both hospital settings and community settings; and 3) provides suggestion that the public should wear the mask during COVID-19 pandemic according to local context. To achieve this goal, government should establish a risk adjusted strategy of mask use to scientifically publicize the use of masks, guarantee sufficient supply of masks, and cooperate for reducing health resources inequities.


title: Limiting factors for wearing personal protective equipment (PPE) in a health care environment evaluated in a randomised study

text: Pandemics and re-emerging diseases put pressure on the health care system to prepare for patient care and sample logistics requiring enhanced personnel protective equipment (PPE) for health care workers. We generated quantifiable data on ergonomics of PPE applicable in a health care setting by defining error rates and physically limiting factors due to PPE-induced restrictions. Nineteen study volunteers tested randomly allocated head- or full body-ventilated PPE suits equipped with powered-air-purifying-respirators and performed four different tasks (two laboratory tutorials, a timed test of selective attention and a test investigating reaction time, mobility, speed and physical exercise) during 6 working hours at 22°C on one day and 4 working hours at 28°C on another day. Error rates and physical parameters (fluid loss, body temperature, heart rate) were determined and ergonomic-related parameters were assessed hourly using assessment sheets. Depending on the PPE system the most restrictive factors, which however had no negative impact on performance (speed and error rate), were: reduced dexterity due to multiple glove layers, impaired visibility by flexible face shields and back pain related to the respirator of the fully ventilated suit. Heat stress and liquid loss were perceived as restrictive at a working temperature of 28°C but not 22°C.


title: Designer Milk

text: Abstract Dairy biotechnology is fast gaining ground in the area of altering milk composition for processing and/or animal and human health by employing nutritional and genetic approaches. Modification of the primary structure of casein, alteration in the lipid profile, increased protein recovery, milk containing nutraceuticals, and replacement for infant formula offer several advantages in the area of processing. Less fat in milk, altered fatty acid profiles to include more healthy fatty acids such as CLA and ω‐fats, improved amino acid profiles, more protein, less lactose, and absence of β‐lactoglobulin (β‐LG) are some opportunities of “designing” milk for human health benefits. Transgenic technology has also produced farm animals that secrete in their milk, human lactoferrin, lysozyme, and lipase so as to simulate human milk in terms of quality and quantity of these elements that are protective to infants. Cow milk allergenicity in children could be reduced by eliminating the β‐LG gene from bovines. Animals that produce milk containing therapeutic agents such as insulin, plasma proteins, drugs, and vaccines for human health have been genetically engineered. In order to cater to animal health, transgenic animals that express in their mammary glands, various components that work against mastitis have been generated. The ultimate acceptability of the “designer” products will depend on ethical issues such as animal welfare and safety, besides better health benefits and increased profitability of products manufactured by the novel techniques.


title: Ensuring Sustainability of Continuous Kidney Replacement Therapy in the Face of Extraordinary Demand: Lessons From the COVID-19 Pandemic

text: With the exponential surge in coronavirus disease 2019 (COVID-19) patients worldwide, the resources needed to provide continuous kidney replacement therapy (CKRT) for patients with acute kidney injury or kidney failure may be threatened. This article summarizes subsisting strategies that can be implemented immediately. Pre-emptive weekly multi-center projections of CKRT demand based on evolving COVID-19 epidemiology and routine workload should be made. Corresponding consumables should be quantified and acquired, with diversification of sources from multiple vendors. Supply procurement should be stepped up accordingly, so that a several-week stock is amassed, with administrative oversight to prevent disproportionate hoarding by institutions. Consumption of CKRT resources can be made more efficient by optimizing circuit anticoagulation to preserve filters, extending use of each vascular access, lowering blood flows to reduce citrate consumption, moderating the CKRT intensity to conserve fluids, or running accelerated KRT at higher clearance to treat more patients per machine. If logistically feasible, earlier transition to intermittent hemodialysis with online generated dialysate, or urgent peritoneal dialysis in selected patients, may help reduce CKRT dependency. These measures, coupled to multi-center collaboration and a corresponding increase in trained medical and nursing staffing levels, may avoid downstream rationing of care and save lives during the peak of the pandemic.


title: The effects of ozone on immune function.

text: A review of the literature reveals that ozone (O3) exposure can either suppress or enhance immune responsiveness. These disparate effects elicited by O3 exposure depend, in large part, on the experimental design used, the immune parameters examined as well as the animal species studied. Despite the apparent contradictions, a general pattern of response to O3 exposure can be recognized. Most studies indicate that continuous O3 exposure leads to an early (days 0-3) impairment of immune responsiveness followed, with continued exposures, by a form of adaptation to O3 that results in a re-establishment of the immune response. The effects of O3 exposure on the response to antigenic stimulation also depend on the time at which O3 exposure occurred. Whereas O3 exposure prior to immunization is without effect on the response to antigen, O3 exposure subsequent to immunization suppresses the response to antigen. Although most studies have focused on immune responses in the lung, numerous investigators have provided functional and anatomical evidence to support the hypothesis that O3 exposure can have profound effects on systemic immunity.


title: Molecular evolution of porcine epidemic diarrhea virus and porcine deltacoronavirus strains in Central China

text: Abstract Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) are epizootic swine viruses. To detect and study the evolution of PEDV and PDCoV in central China (Shanxi, Henan, Hubei province), 70 clinical intestinal and fecal samples from piglets with severe watery diarrhea during August 2015 and June 2016 were collected, tested and analyzed. PEDV was more frequently detected by PCR than PDCoV. Phylogenetic analysis of S genes showed that the 10 PEDV strains from this study clustered into G2a (n = 7) and G2b (n = 3) groups. Additionally, the three G2b strains (PEDV S2△) contained the same specific 3 nt deletion in S2 as other reference strains in G2b. Interestingly, complete genome analysis indicated that CH/hubei/2016 was closer to the US INDEL strain and G2a group. CH/hubei/2016 had one recombination event in S2 gene which may have resulted from AH2012-12 (from G2b group) and CH-ZMDZY-11 (from G2a group). Furthermore, 10 purifying selection sites in S gene indicated an adaptive evolution of PEDV in central China swine herds. These results suggested that Pandemic G2a and G2b are predominant PEDV genotype circulating in central China. In addition, the deletion and recombination identified in S gene suggested PEDV strains of central exhibited an evolutionary variety. However, whether these changes affect the pathogenicity and antigenicity of wild PEDV is unknown and is worth for further investigation.


title: Insurance uptake among small and medium-sized tourism and hospitality enterprises in a resource-scarce environment

text: Abstract Small and medium-sized tourism and hospitality enterprises (SMTHEs) are often susceptible to various hazards, which result in risk concerns. Insurance is recognised as one of the risk management strategies, but evidence indicates that insurance uptake among SMTHEs has been low. Yet, researchers have hardly researched into the factors that influence insurance uptake among SMTHEs. Two-hundred and fifty (250) respondents were selected using a multi-stage sampling technique. Confirmatory factor analysis, multivariate logit and probit regression techniques were used to determine factors underlying SMTHEs' insurance uptake. Risk concerns, the firm's characteristics, the perceived benefits of insurance and other informal risk coping mechanisms, as well as insurance service provision concerns were identified as determinants of insurance uptake. This is one of the first papers to offer a holistic understanding of the factors influencing SMTHEs' insurance subscription in a resource-scarce destination of Sub-Saharan Africa. The practical and theoretical implications of the paper are discussed.


title: Complete sequences of 3′ end coding region for structural protein genes of turkey coronavirus

text: Abstract Overlapping fragments of genomic RNA spanning 6963 nucleotides from 5′ end of spike (S) protein gene to 3′ end of nucleocapsid (N) protein gene of turkey coronavirus (TCoV) were amplified by reverse-transcription-polymerase chain reaction (RT-PCR). The primers were derived from the corresponding sequences of infectious bronchitis virus (IBV). The PCR products were cloned and sequenced and their nucleic acid structure and similarity to published sequences of other coronaviruses were analyzed. Sequencing and subsequent analysis revealed 9 open reading frames (ORFs) representing the entire S protein gene, tricistronic gene 3, membrane (M) protein gene, bicistronic gene 5, and N protein gene in the order of 5′–3′. The overall nucleic acid structures of these encoding regions of TCoV were very similar to the homologous regions of IBV. The consensus transcription-regulating sequence (TRS) of IBV, CT(T/G)AACAA, was highly conserved in TCoV genome at the levels of nucleotide sequence and location in regarding to the initiation codon of individual genes. Pair-wise comparison of gene 3, M gene, gene 5, or N gene sequences with their counterparts of IBV revealed high levels (82.1–92.0%) of similarity. Phylogenetic analysis based on the deduced amino acid sequences of S, M, or N protein demonstrated that TCoV was clustered within the same genomic lineage as the IBV strains while all the other mammalian coronaviruses were grouped into separate clusters corresponding to antigenic groups I or II. There were substantial differences of S protein sequence between TCoV and IBV with only 33.8–33.9% of similarity.


title: Using UPLC-MS/MS for Characterization of Active Components in Extracts of Yupingfeng and Application to a Comparative Pharmacokinetic Study in Rat Plasma after Oral Administration

text: Yupingfeng (YPF), a famous traditional Chinese medicine, which contains a large array of compounds, has been effectually used in health protection. A two-dimensional liquid chromatography ((2)D-LC) combined with quadrupole time-of-flight mass spectrometry (QTOF-MS) method was firstly established to separate and identify chemical components in YPF. A total of 33 compounds were identified, including 15 constituents (flavonoids and saponins) in Astragali radix; seven constituents (sesquiterpenoids and polysaccharide) in Atractylodis rhizoma; and 11 constituents (chromone and coumarins) in Saposhnikoviae radix. The corresponding fragmentation pathway of typical substances was investigated. Then, seven active constituents (astragaloside, calycosin, formononetin, cimicifugoside, 4-O-beta-d-glucosyl-5-O-methylvisamminol, sec-O-glucosylhamaudol, and atractylenolide II) derived from three medicinal plants were chosen to further investigate the pharmacokinetic behavior of YPF formula using ultrahigh-performance liquid chromatography with triple quadrupole mass spectrometry system. The method was sensitive, accurate and reliable. We also used the area under the plasma concentration–time curve from zero to infinity (AUC(0−∞)) as weighting factor to make an integrated pharmacokinetic curve. Results show that the constituents of Saposhnikoviae radix have the best absorption and pharmacokinetic behavior and may play important role in leading to the changes of overall therapeutic effects of YPF. Further study is needed to confirm the association between them.


title: Experimental reproduction of postweaning multisystemic wasting syndrome (PMWS) in pigs in Sweden and Denmark with a Swedish isolate of porcine circovirus type 2

text: Abstract An experimental model using 3-day-old snatch-farrowed colostrum-deprived piglets co-infected with porcine circovirus type 2 (PCV2) and porcine parvovirus (PPV) is at present one of the best methods to study factors affecting development of postweaning multisystemic wasting syndrome (PMWS). A Swedish isolate of PCV2 (S-PCV2) retrieved in 1993 from a healthy pig has been used in this model to reproduce PMWS in pigs from Northern Ireland. This virus has been present in the Swedish pig population for at least a decade without causing any known PMWS disease problems, despite its potential pathogenicity. The reasons for this are unknown, but could be related to genetics, absence of triggers for PCV2 upregulation (infectious agent and/or management forms) within Swedish pig husbandry. In order to confirm the pathogenicity of S-PCV2, Swedish and Danish pigs were experimentally infected with this isolate according to the established model. Swedish pigs were also infected with a reference isolate of PCV2 (PCV2-1010) to compare the severity of disease caused by the two isolates in Swedish pigs. Both Danish and Swedish pigs developed PMWS after the experimental infection with S-PCV2. Antibodies to PCV2 developed later and reached lower levels in serum from pigs infected with S-PCV2 than in pigs inoculated with PCV2-1010. In general, pigs infected with S-PCV2 showed more severe clinical signs of disease than pigs infected with PCV2-1010, but pigs from all PCV2-inoculated groups displayed gross and histological lesions consistent with PMWS. All pigs inoculated with PPV, alone or in combination with PCV2, displayed interleukin-10 responses in serum while only pigs infected with PPV in combination with PCV2 showed interferon-α in serum on repeated occasions. Thus, the pathogenicity of S-PCV2 was confirmed and a role for cytokines in the etiology of PMWS was indicated.


title: Comparative analysis of immune responses following experimental infection of pigs with European porcine reproductive and respiratory syndrome virus strains of differing virulence

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is difficult to control due to a high mutation rate and the emergence of virulent strains. The objective of this study was to analyze the immunological and pathological responses after infection with the European subtype 3 strain Lena in comparison to subtype 1 strains Belgium A and Lelystad-Ter Huurne (LV). Sixteen pigs were inoculated per strain, and sixteen pigs with PBS. At days 7 and 21 post-inoculation (p.i.), four pigs per group were immunized with an Aujeszky disease vaccine (ADV) to study the immune competence after PRRSV infection. Infection with the Lena strain resulted in fever and clinical signs. This was not observed in the Belgium A or LV-infected pigs. Infection with the Lena strain resulted in high virus titers in serum, low numbers of IFN-γ secreting cells, a change in leukocyte populations and a delayed antibody response to immunization with ADV. Levels of IL-1β, IFN-α, IL-10, IL-12, TNF-α and IFN-γ mRNA of the Lena-infected pigs were increased during the first week of infection. For pigs infected with the Belgium A or LV strain, the effects of infection on these parameters were less pronounced, although for the Belgium A-infected pigs, the level of the analyzed cytokines, except for TNF-α, and leukocyte populations were comparable to the Lena-infected pigs. These results suggest that while the outcome of infection for the three strains was comparable, with mostly clearance of viremia at day 33 p.i, differences in immune responses were observed, perhaps contributing to their virulence.


Caring for Caregivers during COVID‐19


title: Debate: Mentalising remotely – The AFNCCF’s adaptations to the coronavirus crisis

text: An overview of the work the approach taken by the Anna Freud National Centre for Children and Families in the rapid transition to remote working in response to the coronavirus lockdown. We outline some of the challenges of remote working and how we are seeking to mitigate them, informed by the over‐riding principle that individual relationships and the experiences of the child, young person and family must remain the central concern. The importance of maintaining a mentalising stance in remote working is discussed. We argue that a mentalising relationship which generates epistemic trust is possible in remote working, but this will require particular thought and effort on the part of the therapist. In particular, it is suggested that mentalising processes can be supported in remote working through, in the absence of the more implicit communications that are possible in face‐to‐face work, more explicit communications about mental states.


title: Clinical presentations and outcomes of patients with Ebola virus disease in Freetown, Sierra Leone

text: BACKGROUND: Clinical and laboratory data were collected and analysed from patients with Ebola virus disease (EVD) in Jui Government Hospital in Freetown, Sierra Leone, where patients with EVD were received and/or treated from October 1, 2014 to March 21, 2015 during the West Africa EVD outbreak. METHODS: The study admitted 285 patients with confirmed EVD and followed them up till the endpoint (recovery or death). EVD was confirmed by quantitative RT-PCR assays detecting blood Ebola virus (EBOV). RESULTS: Among the 285 lab-confirmed EVD cases in Jui Government Hospital, 146 recovered and 139 died, with an overall survival rate of 51.23 %. Patients under the age of 6 years had a lower survival rate (37.50 %). Most non-survivors (79.86 %) died within 7 days after admission and the mean hospitalization time for non-survivors was 5.56 ± 6.11 days. More than half survivors (63.69 %) turned blood EBOV negative within 3 weeks after admission and the mean hospitalization time for survivors was 20.38 ± 7.58 days. High blood viral load (≥10(6) copies/ml) was found to be predictive of the non-survival outcome as indicated by the Receiver Operating Characteristic (ROC) curve analysis. The probability of patients’ survival was less than 15 % when blood viral load was greater than 10(6) copies/ml. Multivariate analyses showed that blood viral load (P = 0.005), confusion (P = 0.010), abdominal pain (P = 0.003), conjunctivitis (P = 0.035), and vomiting (P = 0.004) were factors independently associated with the outcomes of EVD patients. CONCLUSIONS: Most death occurred within 1 week after admission, and patients at the age of 6 or younger had a lower survival rate. Most surviving patients turned blood EBOV negative within 1–4 weeks after admission. Factors such as high blood viral load, confusion, abdominal pain, vomiting and conjunctivitis were associated with poor prognosis for EVD patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0195-9) contains supplementary material, which is available to authorized users.


Mass gatherings medicine: international cooperation and progress


title: Tula hantavirus triggers pro-apoptotic signals of ER stress in Vero E6 cells

text: Abstract Tula virus is a member of the Hantavirus genus of the family Bunyaviridae. Viruses of this family have an unusual pattern of intracellular maturation at the ER–Golgi compartment. We recently found that Tula virus, similar to several other hantaviruses, is able to induce apoptosis in cultured cells [Li, X.D., Kukkonen, S., Vapalahti, O., Plyusnin, A., Lankinen, H., Vaheri, A., 2004. Tula hantavirus infection of Vero E6 cells induces apoptosis involving caspase 8 activation. J. Gen. Virol. 85, 3261–3268.]. However, the cellular mechanisms remain to be clarified. In this study, we demonstrate that the progressive replication of Tula virus in Vero E6 cells initiates several death programs that are intimately associated with ER stress: (1) early activation of ER-resident caspase-12; (2) phosphorylation of Jun NH2-terminal kinase (JNK) and its downstream target transcriptional factor, c-jun; (3) induction of the pro-apoptotic transcriptional factor, growth arrest- and DNA damage-inducible gene 153, or C/EBP homologous protein (Gadd153/chop); and (4) changes in the ER-membrane protein BAP31 implying cross-talk with the mitochondrial apoptosis pathway. Furthermore, we confirmed that a sustained ER stress was induced marked by an increased expression of an ER chaperone Grp78/BiP. Taken together, we have identified involvement of ER stress-mediated death program in Tula virus-infected Vero E6 cells which provides a new approach to understand the mechanisms in hantavirus-induced apoptosis.


title: Burden of tick-borne infections on American companion animals

text: This review examines the dynamics of tick biology and tick-borne infections in the United States. Clinical tick-borne diseases in dogs and cats are discussed. We demonstrate that there is much interest in tickborne infections at the level of the lay public (pet owners), describe trends in the distribution and prevalence of tickborne infections in the U.S., summarize some issues in understanding the degree of ill health due to tickborne infections, and suggest some avenues for research that would clarify these issues.


title: Exacerbations Etiology and Pathophysiologic Mechanisms

text: Some patients with COPD are prone to frequent exacerbations, which are an important determinant of health status. Such patients have elevated airway cytokine levels, suggesting the presence of increased inflammation that may increase their susceptibility to exacerbation. The inflammatory response during a COPD exacerbation is variable, but increases in interleukin-6 levels during the exacerbation are related to the presence of a common cold. Rhinovirus infection is the most important etiologic factor in COPD exacerbations and is an important target for preventive therapy. The reduction of COPD exacerbations will have an important impact on the considerable morbidity and mortality associated with COPD.


Coronaviruses in Balkan nephritis


title: Prediction of endoplasmic reticulum resident proteins using fragmented amino acid composition and support vector machine

text: BACKGROUND: The endoplasmic reticulum plays an important role in many cellular processes, which includes protein synthesis, folding and post-translational processing of newly synthesized proteins. It is also the site for quality control of misfolded proteins and entry point of extracellular proteins to the secretory pathway. Hence at any given point of time, endoplasmic reticulum contains two different cohorts of proteins, (i) proteins involved in endoplasmic reticulum-specific function, which reside in the lumen of the endoplasmic reticulum, called as endoplasmic reticulum resident proteins and (ii) proteins which are in process of moving to the extracellular space. Thus, endoplasmic reticulum resident proteins must somehow be distinguished from newly synthesized secretory proteins, which pass through the endoplasmic reticulum on their way out of the cell. Approximately only 50% of the proteins used in this study as training data had endoplasmic reticulum retention signal, which shows that these signals are not essentially present in all endoplasmic reticulum resident proteins. This also strongly indicates the role of additional factors in retention of endoplasmic reticulum-specific proteins inside the endoplasmic reticulum. METHODS: This is a support vector machine based method, where we had used different forms of protein features as inputs for support vector machine to develop the prediction models. During training leave-one-out approach of cross-validation was used. Maximum performance was obtained with a combination of amino acid compositions of different part of proteins. RESULTS: In this study, we have reported a novel support vector machine based method for predicting endoplasmic reticulum resident proteins, named as ERPred. During training we achieved a maximum accuracy of 81.42% with leave-one-out approach of cross-validation. When evaluated on independent dataset, ERPred did prediction with sensitivity of 72.31% and specificity of 83.69%. We have also annotated six different proteomes to predict the candidate endoplasmic reticulum resident proteins in them. A webserver, ERPred, was developed to make the method available to the scientific community, which can be accessed at http://proteininformatics.org/mkumar/erpred/index.html. DISCUSSION: We found that out of 124 proteins of the training dataset, only 66 proteins had endoplasmic reticulum retention signals, which shows that these signals are not an absolute necessity for endoplasmic reticulum resident proteins to remain inside the endoplasmic reticulum. This observation also strongly indicates the role of additional factors in retention of proteins inside the endoplasmic reticulum. Our proposed predictor, ERPred, is a signal independent tool. It is tuned for the prediction of endoplasmic reticulum resident proteins, even if the query protein does not contain specific ER-retention signal.


title: Prevalence of porcine circovirus type 3 in pigs in the southeastern Chinese province of Zhejiang

text: BACKGROUND: Porcine circovirus type 3 (PCV3) was first reported in US in 2016. The virus was also identified later in China. Prevalence of PCV3 in Zhejiang province in southeastern China is not clear though it has been reported in many parts of China. RESULTS: PCV3 infection and its co-infection with other swine viral pathogens in pig herds of Zhejiang province were retrospectively investigated by quantitative PCR (qPCR) and its sero-prevalence by indirect ELISA. PCV3 was found positive in 67.1% of the 283 clinical samples taken from 2014 to 2017 as shown by qPCR. Single infection with PCV3 accounted for only one-third of the samples, and majority were of co-infections, predominantly with PEDV (41.6%) but generally low with other swine viruses. Indirect ELISA using the PCV3 capsid protein as the coating antigen revealed an average sero-positive rate of 52.6% (40.8 to 60.8%) in 2345 serum samples from 2011 to 2017, with earliest yet high positive findings in samples taken in 2012. Of 203 serum samples, the qPCR method showed more positive findings than ELISA (81.3% vs 56.2%). With 89 serum samples negative by ELISA, vast majority (n = 81) were found positive by qPCR. There was negative correlation in levels of PCV3 DNA and anti-capsid antibody response. ORF2-based phylogenetic analysis revealed three major groups (PCV3a, PCV3b and PCV3c) of the 200 strains, 38 from this study and 162 reference strains from GenBank. Most of the strains from this study were clustered into PCV3c. Of the putative signature residues of the capsid protein (aa 24, 27, 77 and 150) relative to the three groups, only the PCV3a group strains showed a distinct pattern of residues VKSI (95% of the strains), while the other two groups did not have such a ‘signature’ pattern. CONCLUSIONS: Results from this study provided further evidence that the novel virus PCV3 was widely distributed in China and might have emerged in Zhejiang province before 2014, most probably back in 2012 when there was high PCV3 sero-prevalence. PCV3 might be viremic in pigs and could spread by fecal shedding. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-1977-7) contains supplementary material, which is available to authorized users.


title: Co-infection with SARS-CoV-2 and influenza A virus

text: Coronavirus Disease 2019 (COVID-19) infection, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is spreading globally and poses a major public health threat. We reported a case of influenza A virus and SARS-CoV-2 co-infection. As the number of COVID-19 cases increase, it will be necessary to comprehensively evaluate imaging and other clinical findings as well as consider co-infection with other respiratory viruses.


title: The performance of chest CT in evaluating the clinical severity of COVID-19 pneumonia: identifying critical cases based on CT characteristics

text: OBJECTIVES: To assess the clinical severity of COVID-19 pneumonia using qualitative and/or quantitative chest CT indicators and identify the CT characteristics of critical cases. MATERIALS AND METHODS: Fifty-one patients with COVID-19 pneumonia including ordinary cases (group A, n=12), severe cases(group B, n=15) and critical cases (group C, n=24) were retrospectively enrolled. The qualitative and quantitative indicators from chest CT were recorded and compared using Fisher's exact test, one-way ANOVA, Kruskal-Wallis H test and receiver operating characteristic analysis. RESULTS: Depending on the severity of the disease, the number of involved lung segments and lobes, the frequencies of consolidation, crazy-paving pattern and air bronchogram increased in more severe cases. Qualitative indicators including total severity score for the whole lung and total score for crazy-paving and consolidation could distinguish groups B and C from A(69% sensitivity, 83% specificity and 73% accuracy) but were similar between group B and group C. Combined qualitative and quantitative indicators could distinguish these three groups with high sensitivity(B+C vs. A, 90%; C vs. B, 92%), specificity(100%, 87%) and accuracy(92%, 90%). Critical cases had higher total severity score(>10) and higher total score for crazy-paving and consolidation(>4) than ordinary cases, and had higher mean lung density(>-779HU) and full width at half maximum(>128HU) but lower relative volume of normal lung density(≦50%) than ordinary/severe cases. In our critical cases, eight patients with relative volume of normal lung density smaller than 40% received mechanical ventilation for supportive treatment, and two of them had died. CONCLUSION: A rapid, accurate severity assessment of COVID-19 pneumonia based on chest CT would be feasible and could provide help for making management decisions, especially for the critical cases.


title: Chapitre 10 Rhinites, sinusites et rhinosinusites

text: ■. Une douleur faciale unilatérale quotidienne à horaire fixe, s’accompagnant de congestion ou d’obstruction nasale ipsilatérale, évoque une sinusite aiguë. ■. Le diagnostic différentiel principal des sinusites aiguës est l’algie vasculaire de la face (cf. partie 2, fiche « Algie faciale »). ■. Les sinusites maxillaire, frontale et ethmoïdale antérieure se caractérisent par la présence de pus dans le méat moyen ipsilatéral. ■. La radiologie n’est pas nécessaire au diagnostic de sinusite aiguë, mais le devient si les signes ne régressent pas sous traitement en moins d’une semaine. ■. Chez un petit enfant, la présence d’un œdème à l’angle interne de l’œil, s’étendant à la paupière supérieure dans un contexte fébrile, est synonyme d’ethmoïdite aiguë extériorisée. ■. Une sinusite devient chronique après 12 semaines d’évolution. ■. Le diagnostic des sinusites chroniques repose sur l’interrogatoire, l’endoscopie nasale à l’optique et la tomodensitométrie (TDM). ■. Les rhinosinusites chroniques forment un ensemble de pathologies caractérisées par un infiltrat inflammatoire polymorphe auto-entretenu. ■. La polypose nasosinusienne ne constitue que le stade le plus sévère des rhinosinusites chroniques. ■. La maladie de Widal est une maladie métabolique associant polypose nasosinusienne, asthme et intolérance à l’aspirine. ■. Les formes unilatérales de rhinosinusite chronique relèvent plutôt du versant chirurgical du traitement (chirurgie endoscopique des sinus), tandis que les formes bilatérales relèvent plutôt du versant médical.


Comprehensive diagnostics for respiratory virus infections after transplantation or after potential exposure to swine flu A/H1N1: what else is out there?


docid: ekrvozjb

title: Use of a multiplex real-time PCR to study the incidence of human metapneumovirus and human respiratory syncytial virus infections during two winter seasons in a Belgian paediatric hospital

text: ABSTRACT Viruses are an important cause of acute respiratory tract infection (ARTI) in children. This study aimed to develop and evaluate a rapid molecular diagnostic test (duplex real-time PCR) for human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV), and to determine the frequency of these two viruses as causative agents of ARTI in Belgium. Nasopharyngeal aspirates were collected over two winter and spring seasons (November 2003 to May 2004 and November 2004 to May 2005) from children aged <5 years with ARTI (n = 778). The duplex real-time PCR showed a linear range of 104–1010 copies/mL for both hMPV and hRSV. Analysis of the stability of the hRSV and hMPV genomes revealed that nasopharyngeal aspirates could be stored at room temperature for up to 1 month without significant loss of detection. hRSV was detected by antigen testing and by real-time PCR; hMPV was detected by real-time PCR only. The hRSV antigen test was less sensitive than PCR, and failed to detect one-third of the hRSV infections. Overall, 54 (6.9%) and 306 (39.3%) of the 778 samples were positive for hMPV and hRSV, respectively. Both viruses infected young infants, but the mean age of infants infected by hRSV was lower than that of infants infected by hMPV (12 months vs. 17 months, respectively).


title: Viruses and thyroiditis: an update

text: Viral infections are frequently cited as a major environmental factor involved in subacute thyroiditis and autoimmune thyroid diseases This review examines the data related to the role of viruses in the development of thyroiditis. Our research has been focused on human data. We have reviewed virological data for each type of thyroiditis at different levels of evidence; epidemiological data, serological data or research on circulating viruses, direct evidence of thyroid tissue infection. Interpretation of epidemiological and serological data must be cautious as they don't prove that this pathogen is responsible for the disease. However, direct evidence of the presence of viruses or their components in the organ are available for retroviruses (HFV) and mumps in subacute thyroiditis, for retroviruses (HTLV-1, HFV, HIV and SV40) in Graves's disease and for HTLV-1, enterovirus, rubella, mumps virus, HSV, EBV and parvovirus in Hashimoto's thyroiditis. However, it remains to determine whether they are responsible for thyroid diseases or whether they are just innocent bystanders. Further studies are needed to clarify the relationship between viruses and thyroid diseases, in order to develop new strategies for prevention and/or treatment.


Extracorporeal Oxygenation and Coronavirus Disease 2019 Epidemic: Is the Membrane Fail-Safe to Cross Contamination?


title: Membrane-anchored serine proteases in health and disease

text: Serine proteases of the trypsin-like family have long been recognized to be critical effectors of biological processes as diverse as digestion, blood coagulation, fibrinolysis, and immunity. In recent years, a subgroup of these enzymes has been identified that are anchored directly to plasma membranes, either by a carboxy-terminal transmembrane domain (Type I), an amino-terminal transmembrane domain with a cytoplasmic extension (Type II or TTSP), or through a glycosyl-phosphatidylinositol (GPI) linkage. Recent biochemical, cellular, and in vivo analyses have now established that membrane-anchored serine proteases are key pericellular contributors to processes vital for development and the maintenance of homeostasis. This chapter will review our current knowledge of the biological and physiological functions of these proteases, their molecular substrates, and their contributions to disease.


title: The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in vitro models of the human blood–brain barrier

text: As researchers across the globe have focused their attention on understanding SARS-CoV-2, the picture that is emerging is that of a virus that has serious effects on the vasculature in multiple organ systems including the cerebral vasculature. Observed effects on the central nervous system includes neurological symptoms (headache, nausea, dizziness), fatal microclot formation and in rare cases encephalitis. However, our understanding of how the virus causes these mild to severe neurological symptoms and how the cerebral vasculature is impacted remains unclear. Thus, the results presented in this report explored whether deleterious outcomes from the SARS-COV-2 viral spike protein on primary human brain microvascular endothelial cells (hBMVECs) could be observed. First, using postmortem brain tissue, we show that the angiotensin converting enzyme 2 or ACE2 (a known binding target for the SARS-CoV-2 spike protein), is expressed throughout various caliber vessels in the frontal cortex. Additionally, ACE2 was also detectable in primary human brain microvascular endothelial (hBMVEC) maintained under cell culture conditions. Analysis for cell viability revealed that neither the S1, S2 or a truncated form of the S1 containing only the RBD had minimal effects on hBMVEC viability within a 48hr exposure window. However, when the viral spike proteins were introduced into model systems that recapitulate the essential features of the Blood-Brain Barrier (BBB), breach to the barrier was evident in various degrees depending on the spike protein subunit tested. Key to our findings is the demonstration that S1 promotes loss of barrier integrity in an advanced 3D microfluid model of the human BBB, a platform that most closely resembles the human physiological conditions at this CNS interface. Subsequent analysis also showed the ability for SARS-CoV-2 spike proteins to trigger a pro-inflammatory response on brain endothelial cells that may contribute to an altered state of BBB function. Together, these results are the first to show the direct impact that the SARS-CoV-2 spike protein could have on brain endothelial cells; thereby offering a plausible explanation for the neurological consequences seen in COVID-19 patients.