title: Shooting Yourself First in the Foot, then in the Head: Normative Democracy Is Suffocating, and then the Coronavirus Came to Light

text: This text starts with the premise that ‘normative democracy’ has rendered our societies vulnerable and burdened with unaddressed social inequalities. I highlight three central arguments: (1) Social media, and, consequently, citizen engagement are becoming a significant filter that can potentially re-imagine the political, economic, and social worlds, which increasingly bleed over to how we might develop and engage with ‘democracy’; to this end, I introduce a brief case study on the nefarious interpretation of the killing of Jamal Khashoggi in 2018 to underscore the tension points in normative democracy; (2) Capitalism, or neoliberalism, needs to be more fully exposed, interrogated, and confronted if ‘normative, representative, hegemonic, electoral democracy’ is to be re-considered, re-imagined, and re-invented; the perpetuation of social inequalities lays bare the frailty of normative democratic institutions; (3) Covid-19 has exposed the fault lines and fissures of normative democracy, illustrating here the ‘common sense’ ways that power imbalances are sustained, which leaves little room for social solidarity; I present herein the case of the economic/labor dynamic in Quebec during the coronavirus. Ultimately, I believe the quest to re-imagine a more meaningful, critically engaged democracy, especially during a context that is imbued with a political, economic, and public health crisis, cannot be delayed much longer.


title: Rhinovirus-Induced Exacerbations of Asthma and COPD

text: Over the past two decades, increasing evidence has shown that, in patients with chronic airways disease, viral infection is the most common cause of exacerbation. This review will examine the evidence for viral-induced exacerbations of asthma and chronic obstructive lung disease and the potential mechanisms by which viruses cause exacerbations. Attention will be focused on rhinovirus, the most common cause of respiratory exacerbations. Exacerbations due to rhinovirus, which infects relatively few cells in the airway and does not cause the cytotoxicity of other viruses such as influenza or respiratory syncytial virus, are particularly poorly understood. While the innate immune response likely plays a role in rhinovirus-induced exacerbations, its precise role, either adaptive or maladaptive, is debated. Because current treatment strategies are only partially effective, further research examining the cellular and molecular mechanisms underlying viral-induced exacerbations of chronic airways diseases is warranted.


title: The first, holistic immunological model of COVID‐19: implications for prevention, diagnosis, and public health measures

text: The natural history of COVID‐19 caused by SARS‐CoV‐2 is extremely variable, ranging from asymptomatic or mild infection, mainly in children, to multi‐organ failure, eventually fatal, mainly in the eldest. We propose here the first model, explaining how the outcome of first, crucial 10‐15 days after infection, hangs on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, Mannose Binding Lectin ). If SARS‐CoV‐2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm) leading to complications often requiring intensive therapy and being, in some patients, fatal. Low‐moderate physical activity can still be recommended. However, extreme physical activity and hyperventilation during the incubation days and early stages of COVID‐19, facilitates early direct penetration of high numbers of virus particles in the lower airways and the alveoli, without impacting on the airway’s mucosae covered by neutralizing antibodies. This allows the virus bypassing the efficient immune barrier of the upper airways mucosa in already infected, young and otherwise healthy athletes. In conclusion, whether the virus or the adaptative immune response reach the lungs first, is a crucial factor deciding the fate of the patient. This “quantitative and time‐sequence dependent” model has several implications for prevention, diagnosis, and therapy of COVID‐19 at all ages.


title: The great opportunity: Evolutionary applications to medicine and public health

text: Evolutionary biology is an essential basic science for medicine, but few doctors and medical researchers are familiar with its most relevant principles. Most medical schools have geneticists who understand evolution, but few have even one evolutionary biologist to suggest other possible applications. The canyon between evolutionary biology and medicine is wide. The question is whether they offer each other enough to make bridge building worthwhile. What benefits could be expected if evolution were brought fully to bear on the problems of medicine? How would studying medical problems advance evolutionary research? Do doctors need to learn evolution, or is it valuable mainly for researchers? What practical steps will promote the application of evolutionary biology in the areas of medicine where it offers the most? To address these questions, we review current and potential applications of evolutionary biology to medicine and public health. Some evolutionary technologies, such as population genetics, serial transfer production of live vaccines, and phylogenetic analysis, have been widely applied. Other areas, such as infectious disease and aging research, illustrate the dramatic recent progress made possible by evolutionary insights. In still other areas, such as epidemiology, psychiatry, and understanding the regulation of bodily defenses, applying evolutionary principles remains an open opportunity. In addition to the utility of specific applications, an evolutionary perspective fundamentally challenges the prevalent but fundamentally incorrect metaphor of the body as a machine designed by an engineer. Bodies are vulnerable to disease – and remarkably resilient – precisely because they are not machines built from a plan. They are, instead, bundles of compromises shaped by natural selection in small increments to maximize reproduction, not health. Understanding the body as a product of natural selection, not design, offers new research questions and a framework for making medical education more coherent. We conclude with recommendations for actions that would better connect evolutionary biology and medicine in ways that will benefit public health. It is our hope that faculty and students will send this article to their undergraduate and medical school Deans, and that this will initiate discussions about the gap, the great opportunity, and action plans to bring the full power of evolutionary biology to bear on human health problems.


title: Big data, privacy and COVID-19 – learning from humanitarian expertise in data protection

text: The COVID-19 pandemic leads governments around the world to resort to tracking technology and other data-driven tools in order to monitor and curb the spread of SARS-CoV-2. Such large-scale incursion into privacy and data protection is unthinkable during times of normalcy. However, in times of a pandemic the use of location data provided by telecom operators and/or technology companies becomes a viable option. Importantly, legal regulations hardly protect people’s privacy against governmental and corporate misuse. Established privacy regimes are focused on individual consent, and most human rights treaties know derogations from privacy and data protection norms for states of emergency. This leaves little safeguards nor remedies to guarantee individual and collective autonomy. However, the challenge of responsible data use during a crisis is not novel. The humanitarian sector has more than a decade of experience to offer. International organisations and humanitarian actors have developed detailed guidelines on how to use data responsibly under extreme circumstances. This article briefly addresses the legal gap of data protection and privacy during this global crisis. Then it outlines the state of the art in humanitarian practice and academia on data protection and data responsibility during crisis.


title: Detection of COVID-19 Infection from Routine Blood Exams with Machine Learning: A Feasibility Study

text: The COVID-19 pandemia due to the SARS-CoV-2 coronavirus, in its first 4 months since its outbreak, has to date reached more than 200 countries worldwide with more than 2 million confirmed cases (probably a much higher number of infected), and almost 200,000 deaths. Amplification of viral RNA by (real time) reverse transcription polymerase chain reaction (rRT-PCR) is the current gold standard test for confirmation of infection, although it presents known shortcomings: long turnaround times (3-4 hours to generate results), potential shortage of reagents, false-negative rates as large as 15-20%, the need for certified laboratories, expensive equipment and trained personnel. Thus there is a need for alternative, faster, less expensive and more accessible tests. We developed two machine learning classification models using hematochemical values from routine blood exams (namely: white blood cells counts, and the platelets, CRP, AST, ALT, GGT, ALP, LDH plasma levels) drawn from 279 patients who, after being admitted to the San Raffaele Hospital (Milan, Italy) emergency-room with COVID-19 symptoms, were screened with the rRT-PCR test performed on respiratory tract specimens. Of these patients, 177 resulted positive, whereas 102 received a negative response. We have developed two machine learning models, to discriminate between patients who are either positive or negative to the SARS-CoV-2: their accuracy ranges between 82% and 86%, and sensitivity between 92% e 95%, so comparably well with respect to the gold standard. We also developed an interpretable Decision Tree model as a simple decision aid for clinician interpreting blood tests (even off-line) for COVID-19 suspect cases. This study demonstrated the feasibility and clinical soundness of using blood tests analysis and machine learning as an alternative to rRT-PCR for identifying COVID-19 positive patients. This is especially useful in those countries, like developing ones, suffering from shortages of rRT-PCR reagents and specialized laboratories. We made available a Web-based tool for clinical reference and evaluation (This tool is available at https://covid19-blood-ml.herokuapp.com/).


A REVIEW OF VIRAL INFECTIONS OF HORSES


title: Recombinant hemagglutinin produced from Chinese Hamster Ovary (CHO) stable cell clones and a PELC/CpG combination adjuvant for H7N9 subunit vaccine development

text: Abstract The novel H7N9 avian influenza A virus has caused human infections in China since 2013; some isolates from the fifth wave of infections have emerged as highly pathogenic avian influenza viruses. Recombinant hemagglutinin proteins of H7N9 viruses can be rapidly and efficiently produced with low-level biocontainment facilities. In this study, recombinant H7 antigen was obtained from engineered stable clones of Chinese Hamster Ovary (CHO) cells for subsequent large-scale production. The stable CHO cell clones were also adapted to grow in serum-free suspension cultures. To improve the immunogenicity of the recombinant H7 antigens, we evaluated the use of a novel combination adjuvant of PELC and CpG (PELC/CpG) to augment the anti-H7N9 immune responses in mice. We compared the effects with other adjuvants such as alum, AddaVax (MF59-like), and several Toll-like receptor ligands such as R848, CpG, and poly (I:C). With the PELC/CpG combination adjuvant, CHO cell-expressed rH7 antigens containing terminally sialylated complex type N-glycans were able to induce high titers of neutralizing antibodies in sera and conferred protection following live virus challenges. These data indicate that the CHO cell-expressed recombinant H7 antigens and a PELC/CpG combination adjuvant can be used for H7N9 subunit vaccine development.


title: Lifestyle behaviours during the COVID‐19 – time to connect

text: Loneliness and social isolation are associated with poor mental and physical health and may increase the likelihood of common mental disorders (depressive and anxiety disorders), substance use, and cognitive decline1,2 . At this moment, people around the globe have been urged to self-isolate and refrain from social interaction due to the COVID-19 pandemic. From public health and preventative care perspectives, there is a pressing need to provide individuals, communities and health agencies with information and interventions to maintain the healthiest possible lifestyle while in isolation.


title: Statistical methods for characterizing transfusion-related changes in regional oxygenation using Near-infrared spectroscopy (NIRS) in preterm infants

text: Near infrared spectroscopy (NIRS) is an imaging-based diagnostic tool that provides non-invasive and continuous evaluation of regional tissue oxygenation in real-time. In recent years, NIRS has show promise as a useful monitoring technology to help detect relative tissue ischemia that could lead to significant morbidity and mortality in preterm infants. However, some issues inherent in NIRS technology use on neonates, such as wide fluctuation in signals, signal dropout and low limit of detection of the device, pose challenges that may obscure reliable interpretation of the NIRS measurements using current methods of analysis. In this paper, we propose new statistical methods to analyse mesenteric rSO2 (regional oxygenation) produced by NIRS to evaluate oxygenation in intestinal tissues and investigate oxygenation response to red blood cell transfusion (RBC) in preterm infants. We present a mean area under the curve (MAUC) measure and a slope measure to capture the mean rSO2 level and temporal trajectory of rSO2, respectively. Estimation methods are developed for these measures and nonparametric testing procedures are proposed to detect RBC-related changes in mesenteric oxygenation in preterm infants. Through simulation studies, we show that the proposed methods demonstrate improved accuracy in characterizing the mean level and changing pattern of mesenteric rSO2 and also increased statistical power in detecting RBC-related changes, as compared with standard approaches. We apply our methods to a NIRS study in preterm infants receiving RBC transfusion from Emory Univerity to evaluate the pre- and post-transfusion mesenteric oxygenation in preterm infants.


title: SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target

text: Viruses are obligate intracellular microbes that exploit the host metabolic machineries to meet their biosynthetic demands, making these host pathways potential therapeutic targets. Here, by exploring a lipid library, we show that AM580, a retinoid derivative and RAR-α agonist, is highly potent in interrupting the life cycle of diverse viruses including Middle East respiratory syndrome coronavirus and influenza A virus. Using click chemistry, the overexpressed sterol regulatory element binding protein (SREBP) is shown to interact with AM580, which accounts for its broad-spectrum antiviral activity. Mechanistic studies pinpoint multiple SREBP proteolytic processes and SREBP-regulated lipid biosynthesis pathways, including the downstream viral protein palmitoylation and double-membrane vesicles formation, that are indispensable for virus replication. Collectively, our study identifies a basic lipogenic transactivation event with broad relevance to human viral infections and represents SREBP as a potential target for the development of broad-spectrum antiviral strategies.


title: Epidemiological Assessment of Imported Coronavirus Disease 2019 (COVID-19) Cases in the Most Affected City Outside of Hubei Province, Wenzhou, China

text: This decision analytical model describes several key epidemiological features of imported coronavirus disease 2019 (COVID-19) cases in Wenzhou, China.


title: Synthesis, cytostatic and anti-HIV evaluations of the new unsaturated acyclic C-5 pyrimidine nucleoside analogues

text: Abstract A series of the novel C-5 alkynyl pyrimidine nucleoside analogues (1–14) in which the sugar moiety was replaced by the conformationally restricted Z- and E-2-butenyl spacer between the phthalimido and pyrimidine ring were synthesized by using Sonogashira cross-coupling reaction. Cytostatic activity evaluation of the novel compounds showed that E-isomers exhibited, in general, better cytostatic activities than the corresponding Z-isomers. E-isomer 14 exhibited the best cytostatic effect against all evaluated malignant cell lines, particularly against hepatocellular carcinoma (Hep G2, IC50 =4.3μM). However, this compound was also cytotoxic to human normal fibroblasts (WI 38). Its Z-isomer 7 showed highly specific antiproliferative activity against Hep G2 (IC50 =18μM) and no cytotoxicity to WI 38. Moreover, compounds 3, 4 and 14 expressed some marginal inhibitory activity against HIV-1 and HIV-2.


title: Demand for Nonhuman Primate Resources in the Age of Biodefense

text: The demand for nonhuman primates will undoubtedly increase to meet biomedical needs in this current age of biodefense. The availability of funding has increased the research on select agents and has created a requirement to validate results in relevant primate models. This review provides a description of current and potential biological threats that are likely to require nonhuman primates for the development of vaccines and therapeutics. Primates have been an invaluable resource in the dissection of viral disease pathogenesis as well as in testing vaccine efficacy. DNA vaccine approaches have been studied successfully for Ebola, Lassa, and anthrax in nonhuman primate models. Nonhuman primate research with monkeypox has provided insight into the role of cytokines in limiting disease severity. Biodefense research that has focused on select agents of bacterial origin has also benefited from nonhuman primate studies. Rhesus macaques have traditionally been the model of choice for anthrax research and have yielded successful findings in vaccine development. In plague research, African green monkeys have contributed to vaccine development. However, the disadvantages of current vaccines will undoubtedly require the generation of new vaccines, thus increasing the need for nonhuman primate research. Unfortunately, the current biosafety level (BSL)-3 and BSL-4 facilities equipped to perform this research are limited, which may ultimately impede progress in this era of biodefense.


title: CIRUGÍA ELECTIVA DURANTE LA PANDEMIA POR SARS-CoV-2 (COVID-19): ANÁLISIS DE MORBIMORTALIDAD Y RECOMENDACIONES SOBRE PRIORIZACIÓN DE LOS PACIENTES Y MEDIDAS DE SEGURIDAD

text: Resume Introducción: La expansión de la infección por SARS-CoV-2 (COVID-19) ha requerido la adaptación de los hospitales afectados por la pandemia, causando una reducción de la actividad quirúrgica electiva. Material y método: Estudio retrospectivo de pacientes operados durante el mes previo y el pico de la pandemia. Se analizó la tasa de contagio por COVID-19, la gravedad de la infección respiratoria según la Brescia Respiratory COVID-19 Severity Scale, las medidas terapéuticas adoptadas y las complicaciones postoperatorias globales. Resultados: Desde el 17 de febrero hasta el 31 de marzo de 2020 se produjo una reducción progresiva de la actividad quirúrgica, interviniéndose únicamente 213 pacientes: 59 (27,8%) de forma programada por patología tumoral, 97 (45,5%) por patología benigna y 57 (26,7%) de forma urgente. Se produjo un aumento progresivo de la tasa de contagio por COVID-19 con un total de 15 (7%) casos. De los pacientes oncológicos, 10 (16,9%) resultaron afectos; en el grupo de cirugía electiva 1 (1%) y en el grupo de cirugía urgente 4 (7%) (p<0,001). Cinco pacientes presentaron una infección respiratoria grave de los cuales 4 estaban afectos por enfermedad oncológica. Hubo 3 (1,4%) exitus, todos debidos a progresión de la infección respiratoria. Conclusiones: Los pacientes sometidos a cirugía presentaron una elevada tasa de infección por COVID-19 y de complicaciones postoperatorias, sobre todo en los pacientes oncológicos. La puesta en marcha de la de la actividad quirúrgica debe basarse en una priorización de los casos a operar, respetando unas premisas de seguridad y optimización de los recursos disponibles. Abstract Introduction: The spread of the SARS-CoV-2 infection (COVID-19) has required adaptation by hospitals affected by the pandemic, which has caused a reduction in elective surgical activity. Material and method: Retrospective study of patients operated on in the previous month and during the peak of the pandemic. We analysed the COVID-19 infection rate, the severity of respiratory infection according to the Brescia respiratory COVID-19 severity scale (BRCSS), the adopted therapeutic measures and the overall postoperative complications. Results: From 17th February to 31st March 2020, there was a progressive decrease in surgical activity, with only 213 patients operated on. This comprised 59 (27.8%) elective operations for oncological diseases, 97 (45.5%) elective operations for benign diseases and 57 (26.7%) as urgent procedures. There was a progressive increase in the rate of infection by COVID-19, with a total of 15 cases (7%). This included 10 patients (16.9%) in the elective group for oncological disease, 1 (1%) in the elective surgery group for benign disease and 4 (7%) in the urgent surgery group (p <0.001). Five patients presented with a severe respiratory infection, of which 4 were affected by oncological disease. There were 3 deaths (1.4%), which were all due to the worsening of a respiratory infection. Conclusions: The patients undergoing the surgical procedures showed high rates of COVID-19 infection and postoperative complications, especially the patients with oncological diseases. Local resumption of surgical activity must be based on the prioritisation of the cases to be operated on, respecting certain premises of security and optimisation of the available resources.


title: Taste and Smell Impairment in COVID-19: An AAO-HNS Anosmia Reporting Tool-Based Comparative Study

text: OBJECTIVE: To identify the taste and smell impairment in coronavirus disease 2019 (COVID-19)–positive subjects and compare the findings with COVID-19–negative subjects using the American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) Anosmia Reporting Tool. SETTING: Tertiary referral center/COVID-19 pandemic hospital. STUDY DESIGN: Comparative study. SUBJECTS AND METHODS: After power analysis, 128 subjects were divided into 2 groups according to real-time polymerase chain reaction (RT-PCR) COVID-19 testing results. Subjects were called via telephone, and the AAO-HNS Anosmia Reporting Tool was used to collect responses. RESULTS: The mean age of the study group was 38.63 ± 10.08 years. At the time of sampling, rhinorrhea was significantly high in the COVID-19–negative group, whereas those complaints described as “other” were significantly high in the COVID-19–positive group. There was a significant difference in the smell/taste impairment rates of the groups (n = 46% [71.9%] for the COVID-19–positive group vs n = 17 [26.6%] for the COVID-19–negative group, P = .001). For subjects with a smell impairment, anosmia rates did not differ between the groups. The rates of hyposmia and parosmia were significantly high in the COVID-19–positive group. For the subjects with taste impairment, ageusia rates did not differ between groups. The rate of hypogeusia and dysgeusia was significantly high in the COVID-19–positive group. Logistic regression analysis indicates that smell/taste impairment in COVID-19–positive subjects increases the odds ratio by 6.956 (95% CI, 3.16-15.29) times. CONCLUSION: COVID-19–positive subjects are strongly associated with smell/taste impairment.


docid: xsoiidyr

title: The Harrod-Domar Model, the Money Market and the Elasticity of the Investment Demand Curve


title: Cost-effectiveness analysis of oral versus intravenous drip infusion of levofloxacin in the treatment of acute lower respiratory tract infection in Chinese elderly patients

text: AIM: Pharmacoeconomic cost-effectiveness analysis of two different dosage regimens of levofloxacin in the treatment of acute lower respiratory tract infection in elderly patients. METHODS: A total of 108 elderly patients with acute lower respiratory tract infection who visited by our hospital between September 2013 and September 2014 were randomly divided into Group A and Group B, with 54 patients in each group. In Group A, levofloxacin injection was given for continuous intravenous infusion treatment, whereas in Group B, levofloxacin injection and levofloxacin capsule were given as sequential therapy (ST). The period of treatment for both the groups was 10 days, and minimum cost analysis was used to analyze the treatment. RESULTS: Groups A and B had cure rates of 61.1% and 59.3% (P>0.05), effective rates of 88.9% and 83.3% (P>0.05), bacterial clearance rates of 96.3% and 92.6% (P>0.05), and incidence rates of adverse reactions of 7.4% and 3.7% (P>0.05), respectively. Treatment costs of Groups A and B were 1,588 RMB and 1,150 RMB, respectively, whereas the cost-effectiveness of the two groups was at 17.86 and 13.81, respectively (P<0.05). CONCLUSION: Levofloxacin ST had relatively higher cost-effectiveness ratio for the treatment of acute lower respiratory tract infection in elderly patients, especially Chinese.


title: Unstructured Biology of Proteins from Ubiquitin-Proteasome System: Roles in Cancer and Neurodegenerative Diseases

text: The 26S proteasome is a large (~2.5 MDa) protein complex consisting of at least 33 different subunits and many other components, which form the ubiquitin proteasomal system (UPS), an ATP-dependent protein degradation system in the cell. UPS serves as an essential component of the cellular protein surveillance machinery, and its dysfunction leads to cancer, neurodegenerative and immunological disorders. Importantly, the functions and regulations of proteins are governed by the combination of ordered regions, intrinsically disordered protein regions (IDPRs) and molecular recognition features (MoRFs). The structure–function relationships of UPS components have not been identified completely; therefore, in this study, we have carried out the functional intrinsic disorder and MoRF analysis for potential neurodegenerative disease and anti-cancer targets of this pathway. Our report represents the presence of significant intrinsic disorder and disorder-based binding regions in several UPS proteins, such as extraproteasomal polyubiquitin receptors (UBQLN1 and UBQLN2), proteasome-associated polyubiquitin receptors (ADRM1 and PSMD4), deubiquitinating enzymes (DUBs) (ATXN3 and USP14), and ubiquitinating enzymes (E2 (UBE2R2) and E3 (STUB1) enzyme). We believe this study will have implications for the conformation-specific roles of different regions of these proteins. This will lead to a better understanding of the molecular basis of UPS-associated diseases.


Yellow fever outbreaks, vaccine shortages and the Hajj and Olympics: call for global vigilance


title: Novel closed-loop bronchoscopy barrier sheath: value addition for one-lung ventilation during the corona virus disease-2019 pandemic

text: Disclosures, conflicts of interest, funding: None.


title: Neuroprotective Effects of Musk of Muskrat on Transient Focal Cerebral Ischemia in Rats

text: Musk of musk deer has been one of the most precious traditional medicinal materials for treatment of stroke, but trading is prohibited. Musk of muskrat, Ondatra zibethicus, is an accessible substitute for musk of musk deer. However, neuroprotective effects of the musk of muskrat on stroke model are so far unclear. Aim of the study is to determine neuroprotective effects of the musk of muskrat on focal cerebral ischemia. The protective effects against focal cerebral ischemia were evaluated using a model of middle cerebral artery occlusion (90-minute occlusion followed by 24-hour reperfusion). Musk of muskrat was collected from scent bag of muskrat and orally administered at doses of 100 and 300 mg/kg twice at times of 0 and 90 min after occlusion. The effects on sensorimotor dysfunction were investigated by using balance beam test and rotarod test after brain ischemia. The expression of cyclooxygenase-2 (COX-2) was investigated by immunohistochemistry. Oral administration of musk at 300 mg/kg significantly reduced (p<0.001) the infarct volume by 32.4% compared with a vehicle-treated group. Oral administration of musk at 300 mg/kg also ameliorated ischemia-induced spontaneous and vestibule sensorimotor dysfunction in balance beam test and rotarod test compared with control group and COX-2 upregulation. Musk of muskrat may have neuroprotective effects against transient focal cerebral ischemia with recovery of sensorimotor dysfunction. Regarding the immunohistochemistry, the effects of muskrat may be due to anti-inflammatory properties through inhibition of COX-2 expressions.


Mass Surveillance in the Age of COVID-19


COVID-19, End-stage heart failure and outcome: a word caution in causal link determination


title: Angelica keiskei, an emerging medicinal herb with various bioactive constituents and biological activities

text: Angelica keiskei (Miq.) Koidz. (Umbelliferae) has traditionally been used to treat dysuria, dyschezia, and dysgalactia as well as to restore vitality. Recently, the aerial parts of A. keiskei have been consumed as a health food. Various flavonoids, coumarins, phenolics, acetylenes, sesquiterpene, diterpene, and triterpenes were identified as the constituents of A. keiskei. The crude extracts and pure constituents were proven to inhibit tumor growth and ameliorate inflammation, obesity, diabetics, hypertension, and ulcer. The extract also showed anti-thrombotic, anti-oxidative, anti-hyperlipidemic, anti-viral, and anti-bacterial activities. This valuable herb needs to be further studied and developed not only to treat these human diseases but also to improve human health. Currently A. keiskei is commercialized as a health food and additives in health drinks. This article presents a comprehensive review of A. keiskei and its potential place in the improvement of human health.


title: Understanding PRRSV Infection in Porcine Lung Based on Genome-Wide Transcriptome Response Identified by Deep Sequencing

text: Porcine reproductive and respiratory syndrome (PRRS) has been one of the most economically important diseases affecting swine industry worldwide and causes great economic losses each year. PRRS virus (PRRSV) replicates mainly in porcine alveolar macrophages (PAMs) and dendritic cells (DCs) and develops persistent infections, antibody-dependent enhancement (ADE), interstitial pneumonia and immunosuppression. But the molecular mechanisms of PRRSV infection still are poorly understood. Here we report on the first genome-wide host transcriptional responses to classical North American type PRRSV (N-PRRSV) strain CH 1a infection using Solexa/Illumina's digital gene expression (DGE) system, a tag-based high-throughput transcriptome sequencing method, and analyse systematically the relationship between pulmonary gene expression profiles after N-PRRSV infection and infection pathology. Our results suggest that N-PRRSV appeared to utilize multiple strategies for its replication and spread in infected pigs, including subverting host innate immune response, inducing an anti-apoptotic and anti-inflammatory state as well as developing ADE. Upregulation expression of virus-induced pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during N-PRRSV infection processes. N-PRRSV-induced immunosuppression might be mediated by apoptosis of infected cells, which caused depletion of immune cells and induced an anti-inflammatory cytokine response in which they were unable to eradicate the primary infection. Our systems analysis will benefit for better understanding the molecular pathogenesis of N-PRRSV infection, developing novel antiviral therapies and identifying genetic components for swine resistance/susceptibility to PRRS.


title: COVID-19: Shining the Light on Africa

text: COVID-19: Shining the Light on Africa.


title: Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs

text: Porcine reproductive and respiratory syndrome (PRRS) is an economically important disease to pork producers worldwide. Commercially, both live and killed PRRSV vaccines are available to control PRRS, but they are not always successful. Based on the results of mucosal immunization studies in other viral models, a good mucosal vaccine may be an effective way to elicit protective immunity to control PRRS outbreaks. In the present study, mucosal adjuvanticity of Mycobacterium tuberculosis whole cell lysate (Mtb WCL) was evaluated in pigs administered a modified live PRRS virus vaccine (PRRS-MLV) intranasally. A Mtb WCL mediated increase in the frequency of NK cells, CD8(+)and CD4(+) T cells, and γδ T cells in pig lungs were detected. Importantly, an increased and early generation of PRRSV specific neutralizing antibodies were detected in PRRS-MLV+ Mtb WCL compared to pigs inoculated with vaccine alone. In addition, there was an increased secretion of Th1 cytokines (IFNγ and IL-12) that correlated with a reciprocal reduction in the production of immunosuppressive cytokines (IL-10 and TGFβ) as well as T-regulatory cells in pigs vaccinated with PRRS-MLV+ Mtb WCL. Further, a complete rescue in arginase levels in the lungs mediated through Mtb WCL was observed in pigs inoculated with PRRS-MLV. In conclusion, Mtb WCL may be a potent mucosal adjuvant for PRRS-MLV in order to potentiate the anti-PRRSV specific immune responses to control PRRS effectively.


title: Inducing Dose Sparing with Inactivated Polio Virus Formulated in Adjuvant CAF01

text: The development of new low cost inactivated polio virus based vaccines (IPV) is a high priority, and will be required to eradicate polio. In addition, such a vaccine constitutes the only realistic polio vaccine in the post-eradication era. One way to reduce the cost of a vaccine is to increase immunogenicity by use of adjuvants. The CAF01 adjuvant has previously been shown to be a safe and potent adjuvant with several antigens, and here we show that in mice IPV formulated with CAF01 induced increased systemic protective immunity measured by binding and neutralization antibody titers in serum. CAF01 also influenced the kinetics of both the cellular and humoral response against IPV to produce a faster, as well as a stronger, response, dominated by IgG2a, IgG2b, and IgG2c isotypes as well as IPV specific T cells secreting IFN-γ/IL-2. Finally, as intestinal immunity is also a priority of polio vaccines, we present a vaccine strategy based on simultaneous priming at an intradermal and an intramuscular site that generate intestinal immune responses against polio virus. Taken together, the IPV-CAF01 formulation constitutes a new promising vaccine against polio with the ability to generate strong humoral and cellular immunity against the polio virus.


title: Mucosal Vaccines for Biodefense

text: Bioterrorism is the deliberate release of biological toxins, pathogenic viruses, bacteria, parasites, or other infectious agents into the public sphere with the objective of causing panic, illness, and/or death on a local, regional, or possibly national scale. The list of potential biological agents compiled by the Centers for Disease Control and Prevention is long and diverse. However, a trait common to virtually all the potential bioterrorism agents is the fact that they are likely to be disseminated by either aerosol or in food/water supplies with the intention of targeting the mucosal surfaces of the respiratory or gastrointestinal tracts, respectively. In some instances, inhalation or ingestion would mimic the natural route by which humans are exposed to these agents. In other instances, (e.g., the inhalation of a toxin is normally associated with food borne illness), it would represent an unnatural route of exposure. For most potential bioterrorism agents, the respiratory or gastrointestinal mucosa may simply serve as a route of entry by which they gain access to the systemic compartment where intoxication/replication occurs. For others, however, the respiratory or gastrointestinal mucosa is the primary tissue associated with pathogenesis, and therefore, the tissue for which countermeasures must be developed.


title: Development and evaluation of loop‐mediated isothermal amplification assay for rapid and sensitive detection of canine parvovirus DNA directly in faecal specimens

text: Aims: To develop a specific and highly sensitive loop‐mediated isothermal amplification (LAMP) technique for the rapid detection of canine parvovirus (CPV) DNA directly in suspected faecal samples of dogs by employing a simple method of template preparation. Methods and Results: LAMP reaction was developed by designing two sets of outer and inner primers, which target a total of six distinct regions on VP2 gene of CPV. The template DNA was prepared by a simple boiling and chilling method. Of the 140 faecal samples screened by the developed LAMP and the conventional PCR assays, 104 samples (74·28%) were found positive by LAMP, whereas 81 samples (57·85%) were found positive by PCR. The specificity of the LAMP assay was tested by cross‐examination of common pathogens of dogs and further confirmed by sequencing. The detection limit of the LAMP was 0·0001 TCID(50) ml(−1), whereas the detection limit of the PCR was 1000 TCID(50) ml(−1). Conclusions: The developed LAMP assay detects CPV DNA in faecal specimens directly within an hour by following a simple and rapid boiling and chilling method of template preparation. The result also shows that the developed LAMP assay is specific and highly sensitive in detecting CPV. Significance and Impact of the Study: The result indicates the potential usefulness of LAMP which is a simple, rapid, specific, highly sensitive and cost‐effective field‐based method for direct detection of CPV from the suspected faecal samples of dogs.


title: Morbid Obesity as an Independent Risk Factor for COVID‐19 Mortality in Hospitalized Patients Younger than 50

text: OBJECTIVE: COVID‐19 continues to spread and younger patients are also being critically affected. This study analyzed obesity as an independent risk factor for mortality in hospitalized patients younger than fifty. METHODS: We retrospectively analyzed data of COVID‐19 patients hospitalized to a large academic hospital system in New York City between March 1st and May 17th, 2020. Data included demographics, comorbidities, BMI and smoking status. Obesity groups included: BMI 30–40 kg/m(2) and BMI ≥ 40 kg/m(2). Multivariable logistic regression models identified variables independently associated with mortality in patients younger and older than 50. RESULTS: Overall, 3,406 patients were included. 572 (17.0%) of the patients were younger than 50. In the younger age group, 60 (10.5%) patients died. In the older age group, 1,076 (38.0%) patients died. For the younger population, BMI above 40 kg/m(2) was independently associated with mortality (aOR 5.1, 95% CI 2.3–11.1). For the older population, BMI above 40 kg/m2 was also independently associated with mortality to a lesser extent (aOR 1.6, 95% CI 1.2 – 2.3). CONCLUSION: Our study demonstrates that hospitalized patients younger than 50 with morbid obesity are more likely to die from COVID‐19. This is particularly relevant in the western world where obesity rates are high.


title: Transspecies Transmission of Gammaretroviruses and the Origin of the Gibbon Ape Leukaemia Virus (GaLV) and the Koala Retrovirus (KoRV)

text: Transspecies transmission of retroviruses is a frequent event, and the human immunodeficiency virus-1 (HIV-1) is a well-known example. The gibbon ape leukaemia virus (GaLV) and koala retrovirus (KoRV), two gammaretroviruses, are also the result of a transspecies transmission, however from a still unknown host. Related retroviruses have been found in Southeast Asian mice although the sequence similarity was limited. Viruses with a higher sequence homology were isolated from Melomys burtoni, the Australian and Indonesian grassland melomys. However, only the habitats of the koalas and the grassland melomys in Australia are overlapping, indicating that the melomys virus may not be the precursor of the GaLV. Viruses closely related to GaLV/KoRV were also detected in bats. Therefore, given the fact that the habitats of the gibbons in Thailand and the koalas in Australia are far away, and that bats are able to fly over long distances, the hypothesis that retroviruses of bats are the origin of GaLV and KoRV deserves consideration. Analysis of previous transspecies transmissions of retroviruses may help to evaluate the potential of transmission of related retroviruses in the future, e.g., that of porcine endogenous retroviruses (PERVs) during xenotransplantation using pig cells, tissues or organs.


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title: Cocooning is essential to relaxing social distancing

text: As the first wave of COVID-19 recedes, policymakers are contemplating the relaxation of shelter-in-place orders. Using a model capturing high-risk populations and transmission rates estimated from hospitalization data, we find that postponing relaxation will only delay a second wave and cocooning vulnerable populations is needed to prevent overwhelming medical surges.


Can Glycyrrhiza glabra L. reduce both upper gastrointestinal tract bleeding and ventilator‐associated pneumonia in intensive‐care unit patients?


title: Detection of multiple viral and bacterial infections in acute exacerbation of chronic obstructive pulmonary disease: A pilot prospective study

text: Few studies have evaluated the contribution of multiple virus and bacterial infections in acute exacerbation of chronic obstructive pulmonary disease. This study estimated the burden of multiple viral and bacterial respiratory infections in moderate to very severe chronic obstructive pulmonary disease patients that were prospectively followed‐up during a 12‐month pilot study. Clinical data were collected monthly and sputum was collected at the time of each acute exacerbation event. Classical culture techniques for bacteria and multiplex polymerase chain reaction (PCR) and microarray detection assays were performed to identify viral and atypical bacterial pathogens in the sputum. Overall, 51 patients were included and 45 acute exacerbation events were investigated clinically and microbiologically. Among the 45 acute exacerbation events, 44% had evidence of viral infection involving human rhinovirus (HRV) and metapneumovirus (hMPV) in 20% and 18%, respectively. Intracellular bacteria were not found in sputum by PCR. Common bacterial pathogens were identified in 42% of acute exacerbation patients, most frequently Branhamella catarrhalis, Streptococcus pneumoniae and Haemophilus influenzae. Viral or virus and bacteria co‐infections were detected in 27% of acute exacerbation events (n = 12) with HRV and hMPV involved in 92% of cases. Patients with co‐infections did not present greater clinical severity scores at exacerbation and more recurrence of acute exacerbation events at 3 and 6 months than those with single infections (P > 0.4). These results suggest that HRV and hMPV may be contributors or cofactors of AECOPD. These findings indicate that viral or virus and bacterial co‐infections do not impact significantly on the clinical severity of acute exacerbation of chronic obstructive pulmonary disease and recurrence at 3 and 6 months. J. Med. Virol. 85:866–873, 2013. © 2013 Wiley Periodicals, Inc.


The emerging HIV epidemic among men who have sex with men in Taiwan


title: Change in practice in gynecologic oncology during the COVID-19 pandemic: a social media survey

text: OBJECTIVE: COVID-19 has affected gynecologic cancer management. The goal of this survey was to evaluate changes that occurred in gynecologic oncology practice during the COVID-19 pandemic. METHODS: A anonymous survey consisting of 33 questions (https://sites.google.com/view/gyncacovidfmartinelli) regarding interaction between gynecologic cancers and COVID-19 was distributed online via social media from April 9 to April 30, 2020. Basic descriptive statistics were applied. Analytics of survey-diffusion and generated-interest (visualizations, engagement rates, response rate) were analyzed. RESULTS: The survey received 20 836 visualizations, generating an average engagement rates by reach of 4.7%. The response rate was 30%. A total of 86% of respondents completed the survey, for a total of 187 physicians surveyed across 49 countries. The majority (143/187; 76%) were gynecologic oncologists, and most were ≤50 years old (146/187; 78%). A total of 49.7% (93/187) were facing the early phase of the COVID-19 pandemic, while 26.7% (50/187) and 23.5% (44/187) were in the peak and plateau phases, respectively. For 97.3% (182/187) of respondents COVID-19 affected or changed their respective clinical practice. Between 16% (27/165) (before surgery) and 25% (26/102) (before medical treatment) did not perform any tests to rule out COVID-19 infection among patients. The majority of respondents did not alter indications of treatment if patients were COVID-19-negative, while treatments were generally postponed in COVID-19-positive patients. Treatments were considered priority for: early stage high-risk uterine cancers (85/187; 45%), newly diagnosed epithelial ovarian cancer (76/187; 41%), and locally advanced cervical cancer (76/187; 41%). Treatment of early stage low-grade endometrioid endometrial cancer was deferred according to 49% (91/187) of respondents, with hormonal treatment as the option of therapy (31%; 56/178). A total of 77% (136/177) of respondents reported no changes in (surgical) treatment for early stage cervical cancer in COVID-19-negative patients, while treatment was postponed by 54% (96/177) of respondent, if the patient tested COVID-19-positive. Neoadjuvant chemotherapy for advanced ovarian cancers was considered by over one-third of respondents as well as hypofractionation of radiation treatment for locally advanced cervical cancers. CONCLUSION: COVID-19 affected the treatment of gynecologic cancers patients, both in terms of prioritization and identification of strategies to reduce hospital access and length of stay. Social media is a reliable tool to perform fast-tracking, worldwide surveys.


COVID-19: A United Kingdom National Health Service cardiology perspective.


title: Antileishmanial activity of MDL 28170, a potent calpain inhibitor

text: Abstract Several calpain inhibitors are under development and some are useful agents against important human pathogens. We therefore investigated the effect of MDL 28170, a potent calpain inhibitor, on the growth of Leishmania amazonensis. After 48h of treatment, the inhibitor exhibited a dose-dependent antileishmanial activity, with a 50% lethal dose (LD50) of 23.3μM. The inhibitor promoted cellular alterations, such as the parasites becoming short and round. A calpain-like protein migrating at 80kDa was identified by Western blotting. In addition, the calpain-like molecules were identified on the cell surface of the flagellate. These results add new in vitro insights into the exploitation of calpain inhibitors in treating parasitic infections and add this family of peptidases to the list of potential targets for development of more potent and specific inhibitors against trypanosomatids.


title: Lactoferrin is an important factor when breastfeeding and COVID‐19 are considered

text: The COVID-19 pandemic raises issues about breastfeeding when mothers have tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We don't know whether the virus can be passed to a foetus or baby during pregnancy or delivery and it has not been found in amniotic fluid or breastmilk (1). Separating babies from virus positive mothers make breastfeeding problematic and could prevent possible protection against viruses (2).


title: A machine learning forecasting model for COVID-19 pandemic in India

text: Coronavirus disease (COVID-19) is an inflammation disease from a new virus. The disease causes respiratory ailment (like influenza) with manifestations, for example, cold, cough and fever, and in progressively serious cases, the problem in breathing. COVID-2019 has been perceived as a worldwide pandemic and a few examinations are being led utilizing different numerical models to anticipate the likely advancement of this pestilence. These numerical models dependent on different factors and investigations are dependent upon potential inclination. Here, we presented a model that could be useful to predict the spread of COVID-2019. We have performed linear regression, Multilayer perceptron and Vector autoregression method for desire on the COVID-19 Kaggle data to anticipate the epidemiological example of the ailment and pace of COVID-2019 cases in India. Anticipated the potential patterns of COVID-19 effects in India dependent on data gathered from Kaggle. With the common data about confirmed, death and recovered cases across India for over the time length helps in anticipating and estimating the not so distant future. For extra assessment or future perspective, case definition and data combination must be kept up persistently.


title: Acute hemorrhage after intra-cerebral biopsy in COVID-19 patients: a report of 3 cases

text: Abstract Background When Belgium’s COVID-19 outbreak began in March of 2020, our neurosurgical department followed the protocol of most surgical departments in the world and postponed elective surgery. However, patients with tumor-like brain lesions requiring urgent surgery still received treatment as usual, in order to ensure ongoing neuro-oncological care. From a series of 31 patients admitted for brain surgery, three were confirmed as infected by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Case description We present the clinical outcomes of these three COVID-19 patients, who underwent an intra-cerebral biopsy in our department during April of 2020. All suffered from a diffuse intra-parenchymal hemorrhage post-operatively. Unfortunately, we were not able to identify a clear etiology of these post-operative complications. It could be hypothesized that an active COVID-19 infection status may be related to a higher bleeding risk. The remaining 28 neuro-oncological non-COVID patients underwent uneventful surgery during the same period. Conclusions This case series reports the previously unreported and unexpected outcomes of COVID-19 patients suffering from acute hemorrhage after intra-cerebral biopsy procedures. Although no direct relation can yet be established, we recommend the neurosurgical community be cautious in such cases.


title: Daphne Genkwa Sieb. et Zucc. Water-Soluble Extracts Act on Enterovirus 71 by Inhibiting Viral Entry

text: Dried flowers of Daphne genkwa Sieb. et Zucc. (Thymelaeaceae) are a Chinese herbal medicine used as an abortifacient with purgative, diuretic and anti-inflammatory activities. However, the activity of this medicine against enteroviral infections has not been investigated. The water-extract of dried buds of D. genkwa Sieb. et Zucc. (DGFW) was examined against various strains of enterovirus 71 (EV71) by neutralization assay, and its initial mode of action was characterized by time-of-addition assay followed by attachment and penetration assays. Pretreatment of DGFW with virus abolished viral replication, indicating that DGFW inhibits EV71 by targeting the virus. GFW exerts its anti-EV71 effects by inhibiting viral entry without producing cytotoxic side effects and thus provides a potential agent for antiviral chemotherapeutics.


title: Incidence of Respiratory Viral Infections Detected by PCR and Real-Time PCR in Adult Patients with Community-Acquired Pneumonia: A Meta-Analysis

text: BACKGROUND: With the development of more rapid and sensitive detection methods based on PCR techniques, the contributions of respiratory viral infections to community-acquired pneumonia (CAP) in adult patients are being more and more recognized. Yet, up to now, there has been a lack of synthetic data that clearly demonstrates the incidence of respiratory viral infections in adult patients with CAP. OBJECTIVES: We intended to demonstrate the incidence of respiratory viral infections detected by PCR and real-time PCR in adult patients with CAP. METHODS: We searched PubMed and Embase for studies providing the incidence of respiratory viral infections in adult patients with CAP. We investigated potential sources of heterogeneity by a univariant metaregression analysis and calculated the combined incidence of viral infections, viral infections mixed with other pathogens and individual respiratory virus species. RESULTS: We eventually identified 23 eligible reports with a total number of 6,404 patients. Incidences ranged from 8.6 to 56.2% for overall respiratory viral infections. We noted significant heterogeneity in incidence estimates for the incidence of viral infections (Cochran's χ(2) = 269.9, p < 0.0001, I(2) = 91.8%). The combined incidence of viral infections was 22.4% (95% CI = 19.0-25.7). Incidences of viral coinfections with other pathogens ranged from 3 to 28%. A high level of heterogeneity was identified as well during the estimates for incidences of coinfections (χ(2) = 200.9, p < 0.0001, I(2) = 91.5%). The combined incidence of viral coinfections with other pathogens was 12.4% (95% CI = 9.7-15.0). Our heterogeneity analyses suggested that a lower respiratory tract sample was associated with higher overall viral incidence. Moreover, the influenza virus, rhinovirus and coronavirus were the 3 most frequently detected viral pathogens in adult patients with CAP according to our study. CONCLUSIONS: Respiratory viruses are probably crucial pathogens of adult patients with CAP, with the influenza virus being the most frequent viral pathogen identified. More than half of the viral infections are characterized as mixed infections with other pathogens.


title: Do expectations of future wealth increase outbound tourism? Evidence from Korea

text: As international tourism is generally considered a luxury good, models to date have shared an understanding that demand is dependent on discretionary income. However, consumption theories predict that a shift in demand can be induced without changes in actual earnings when expectations for future income are adjusted. This presumes demand for international tourism can be influenced by “wealth effects” from real estate and financial assets. This study tested for the wealth effect on Korean outbound travelers during the 20 years between 1989 and 2009. Korea is a unique place to examine in that Korean households possess housing assets and financial assets that are traded actively in markets. The results of this study favored the possibility of a significant wealth effect from housing on outbound travel demand, but not from financial assets. This may be explained by data sensitivity and the relative importance of financial assets in the Korean people's wealth portfolios. Implications and suggestions for future research are provided along with the findings of the study.


title: 50 Infectious Disease Considerations for the Operating Room

text: Abstract The risk of infection transmission by anesthesia providers in their work area environment is reviewed. The dynamics of transmission and the strategies for preventing infection transmission in health care institutions are discussed. Anesthesiologists have long been patient safety advocates and have taken on increasing responsibility for preventing health care–associated infections. Anesthesia providers practice in a nonsterile environment within the operating room and have an impact on bacterial transmission and infection rates. Understanding the characteristics of transmission elements provides the practicing anesthesiologist with methods to protect susceptible patients and themselves to avoid spreading infection. It is vital to have in place proper systems to remove contaminated air to minimize the risk of airborne pathogens being transmitted by children. Preoperative patient skin and other bacterial reservoir decontamination and hand hygiene by anesthesia providers reduces contamination of the work area and IV access ports. Hand hygiene is a well-known and effective solution to the problem of bacterial transmission within and across patients and is considered the most important and cost-effective individual intervention in the prevention of health care–associated infections in children and health care providers Compliance with the current “5 moments” World Health Organization guidelines could make a major inroad into reducing provider hand and workspace contamination. Surgical antimicrobial prophylaxis is an essential tool to reduce the risk of postoperative infections, and the anesthesia team plays a central role in ensuring the proper timing of drug administration. Protocols, although effective, require continuous feedback and revision.


title: Clinical characteristics and viral load of respiratory syncytial virus and human metapneumovirus in children hospitaled for acute lower respiratory tract infection

text: Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two common viral pathogens in acute lower respiratory tract infections (ALRTI). However, the association of viral load with clinical characteristics is not well‐defined in ALRTI. To explore the correlation between viral load and clinical characteristics of RSV and HMPV in children hospitalized for ALRTI in Lanzhou, China. Three hundred and eighty‐seven children hospitalized for ALRTI were enrolled. Nasopharyngeal aspirates (NPAs) were sampled from each children. Real‐time PCR was used to screen RSV, HMPV, and twelve additional respiratory viruses. Bronchiolitis was the leading diagnoses both in RSV and HMPV positive patients. A significantly greater frequency of wheezing (52% vs. 33.52%, P = 0.000) was noted in RSV positive and negative patients. The RSV viral load was significant higher in children aged <1 year (P = 0.003), children without fever and wheezing (P = 0.015 and P = 0.000), days of illness <14 days (P = 0.002), children with bronchiolitis (P = 0.012) and children with RSV single infections (P = 0.000). No difference was found in the clinical features of HMPV positive and negative patients. The HMPV viral load had no correlation with any clinical characteristics. The incidences of severe disease were similar between single infection and coinfection for the two viruses (RSV, P = 0.221; HMPV, P = 0.764) and there has no statistical significance between severity and viral load (P = 0.166 and P = 0.721). Bronchiolitis is the most common disease caused by RSV and HMPV. High viral load or co‐infection may be associated with some symptoms but neither has a significant impact on disease severity for the two viruses. J. Med. Virol. 89:589–597, 2017. © 2016 Wiley Periodicals, Inc.


title: In Vitro Evaluation of Curcumin-Encapsulated Chitosan Nanoparticles against Feline Infectious Peritonitis Virus and Pharmacokinetics Study in Cats

text: Feline infectious peritonitis (FIP) is an important feline viral disease, causing an overridden inflammatory response that results in a high mortality rate, primarily in young cats. Curcumin is notable for its biological activities against various viral diseases; however, its poor bioavailability has hindered its potential in therapeutic application. In this study, curcumin was encapsulated in chitosan nanoparticles to improve its bioavailability. Curcumin-encapsulated chitosan (Cur-CS) nanoparticles were synthesised based on the ionic gelation technique and were spherical and cuboidal in shape, with an average particle size of 330 nm and +42 mV in zeta potential. The nanoparticles exerted lower toxicity in Crandell-Rees feline kidney (CrFK) cells and enhanced antiviral activities with a selective index (SI) value three times higher than that of curcumin. Feline-specific bead-based multiplex immunoassay and qPCR were used to examine their modulatory effects on proinflammatory cytokines, including tumour necrosis factor (TNF)α, interleukin- (IL-) 6, and IL-1β. There were significant decrements in IL-1β, IL-6, and TNFα expression in both curcumin and Cur-CS nanoparticles. Based on the multiplex immunoassay, curcumin and the Cur-CS nanoparticles could lower the immune-related proteins in FIP virus (FIPV) infection. The single- and multiple-dose pharmacokinetics profiles of curcumin and the Cur-CS nanoparticles were determined by high-performance liquid chromatography (HPLC). Oral delivery of the Cur-CS nanoparticles to cats showed enhanced bioavailability with a maximum plasma concentration (C(max)) value of 621.5 ng/mL. Incorporating chitosan nanoparticles to deliver curcumin improved the oral bioavailability and antiviral effects of curcumin against FIPV infection. This study provides evidence for the potential of Cur-CS nanoparticles as a supplementary treatment of FIP.


title: Networking of Public Health Microbiology Laboratories Bolsters Europe’s Defenses against Infectious Diseases

text: In an era of global health threats caused by epidemics of infectious diseases and rising multidrug resistance, microbiology laboratories provide essential scientific evidence for risk assessment, prevention, and control. Microbiology has been at the core of European infectious disease surveillance networks for decades. Since 2010, these networks have been coordinated by the European Centre for Disease Prevention and Control (ECDC). Activities delivered in these networks include harmonization of laboratory diagnostic, antimicrobial susceptibility and molecular typing methods, multicentre method validation, technical capacity mapping, training of laboratory staff, and continuing quality assessment of laboratory testing. Cooperation among the European laboratory networks in the past 7 years has proved successful in strengthening epidemic preparedness by enabling adaptive capabilities for rapid detection of emerging pathogens across Europe. In partnership with food safety authorities, international public health agencies and learned societies, ECDC-supported laboratory networks have also progressed harmonization of routinely used antimicrobial susceptibility and molecular typing methods, thereby significantly advancing the quality, comparability and precision of microbiological information gathered by ECDC for surveillance for zoonotic diseases and multidrug-resistant pathogens in Europe. ECDC continues to act as a catalyst for sustaining continuous practice improvements and strengthening wider access to laboratory capacity across the European Union. Key priorities include optimization and broader use of rapid diagnostics, further integration of whole-genome sequencing in surveillance and electronic linkage of laboratory and public health systems. This article highlights some of the network contributions to public health in Europe and the role that ECDC plays managing these networks.


title: Microbiology of Cystic Fibrosis Airway Disease

text: Although survival of individuals with cystic fibrosis (CF) has been continuously improving for the past 40 years, respiratory failure secondary to recurrent pulmonary infections remains the leading cause of mortality in this patient population. Certain pathogens such as Pseudomonas aeruginosa , methicillin-resistant Staphylococcus aureus , and species of the Burkholderia cepacia complex continue to be associated with poorer clinical outcomes including accelerated lung function decline and increased mortality. In addition, other organisms such as anaerobes, viruses, and fungi are increasingly recognized as potential contributors to disease progression. Culture-independent molecular methods are also being used for diagnostic purposes and to examine the interaction of microorganisms in the CF airway. Given the importance of CF airway infections, ongoing initiatives to promote understanding of the epidemiology, clinical course, and treatment options for these infections are needed.


COVID-19 and artificial intelligence: protecting health-care workers and curbing the spread


Three steps to flatten the mental health need curve amid the COVID‐19 pandemic


title: Laboratory diagnosis and surveillance of human respiratory viruses by PCR in Victoria, Australia, 2002–2003

text: Respiratory viruses were identified by the polymerase chain reaction (PCR) in more than 4,200 specimens collected during 2002 and 2003 in Victoria, Australia from patients admitted to hospitals or participating in an influenza surveillance program. Influenza viruses and picornaviruses were important causes of morbidity in both years. Additional testing of picornavirus‐positive samples suggested that rhinoviruses but not enteroviruses were more likely to be associated with respiratory symptoms, irrespective of the season in which they circulated. Detection of influenza viruses was strongly associated with the clinical symptoms of cough, fever, and fatigue; but each of the other respiratory viruses occasionally caused these symptoms or was responsible for symptoms severe enough to require hospitalization. Human coronaviruses HCoV‐OC43 and HCoV‐229E circulated at low levels throughout the study period with peak activity in winter, but overall did not circulate as widely as has often been reported for these agents. Evidence for the human metapneumovirus (hMPV) was only sought in the second year of the study and revealed low‐level circulation of this virus, mainly in the cooler months among the very young and adult populations. The detection rate of all viruses declined with increasing age of the patient, particularly in hospital patients. Infection with more than one respiratory virus occurred in a small number of patients; picornaviruses were most commonly implicated in these dual infections. J. Med. Virol. 75:122–129, 2005. © 2005 Wiley‐Liss, Inc.


title: CRISPR-Cas13a mediated nanosystem for attomolar detection of canine parvovirus type 2

text: Canine parvovirus type 2 (CPV-2) infection is the most lethal disease of dogs with higher mortality in puppies worldwide. In today’s world, dogs are an integral part of our communities as well as dogs breeding and rearing has become a lucrative business. Therefore, a fast, accurate, portable, and cost-effective CPV-2 detection method with the ability for on-site detection is highly desired. In this study, we for the first time proposed a nanosystem for CPV-2 DNA detection with RNA-guided RNA endonuclease Cas13a, which upon activation results in collateral RNA degradation. We expressed LwCas13a in prokaryotic expression system and purified it through nickel column. Activity of Cas13a was verified by RNA-bound fluorescent group while using a quenched fluorescent probe as signals. Further Cas13a was combined with Recombinase polymerase amplification (RPA) and T7 transcription to establish molecular detection system termed specific high-sensitivity enzymatic reporter un-locking (SHERLOCK) for sensitive detection of CPV-2 DNA. This nanosystem can detect 100 amol/L CPV-2 DNA within 30 min. The proposed nanosystem exhibited high specificity when tested for CPV-2 and other dog viruses. This CRISPR-Cas13a mediated sensitive detection approach can be of formidable advantage during CPV-2 outbreaks because it is time-efficient, less laborious and does not involve the use of sophisticated instruments.


title: Pooling of nasopharyngeal swab specimens for SARS‐CoV‐2 detection by RT‐PCR

text: Until an effective vaccine is available, interruption of community circulation of SARS- CoV-2 is crucial to control virus spread. To this end, systematic testing of large population groups by RT-PCR is mandatory to case identification and contact tracing thereby minimizing the likelihood of resurgence in contagion.1 This article is protected by copyright. All rights reserved.


title: Dual priming oligonucleotide (DPO)-based real-time RT-PCR assay for accurate differentiation of four major viruses causing porcine viral diarrhea

text: Abstract Currently in China, porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine rotavirus (PoRV), and porcine deltacoronavirus (PDCoV) are the major causes of porcine viral diarrhea, and mixed infections in clinics are common, resulting in significant economic losses in pig industry. Here, a dual priming oligonucleotide (DPO)-based multiplex real-time SYBR Green RT-PCR assay were developed for accurately differentiating PEDV, TGEV, PoRV, and PDCoV in clinical specimens targeting the N gene of TGEV, PEDV, and PDCoV, and the VP7 gene of PoRV. Results showed that the DPO primer allowed a wider annealing temperature range (40–65 °C) and had a higher priming specificity compared to conventional primer, in which more than 3 nucleotides in the 3′- or 5′-segment of DPO primer mismatched with DNA template, PCR amplification efficiency would decrease substantially or extension would not proceed. DPO-based multiplex real-time RT-PCR method had analytical detection limit of 8.63 × 102 copies/μL, 1.92 × 102 copies/μL, 1.74 × 102 copies/μL, and 1.76 × 102 copies/μL for PEDV, TGEV, PoRV, and PDCoV in clinical specimens, respectively. A total of 672 clinical specimens of piglets with diarrheal symptoms were collected in Northeastern China from 2017 to 2018 followed by analysis using the assay, and epidemiological investigation results showed that PEDV, TGEV, PoRV, and PDCoV prevalence was 19.05%, 5.21%, 4.32%, and 3.87%, respectively. The assay developed in this study showed higher detection accuracy than conventional RT-PCR method, suggesting a useful tool for the accurate differentiation of the four major viruses causing porcine viral diarrhea in practice.


title: Strong evolutionary convergence of receptor-binding protein spike between COVID-19 and SARS-related coronaviruses

text: Coronavirus Disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS)-related coronaviruses (e.g., 2019-nCoV and SARS-CoV) are phylogenetically distantly related, but both are capable of infecting human hosts via the same receptor, angiotensin-converting enzyme 2, and cause similar clinical and pathological features, suggesting their phenotypic convergence. Yet, the molecular basis that underlies their phenotypic convergence remains unknown. Here, we used a recently developed molecular phyloecological approach to examine the molecular basis leading to their phenotypic convergence. Our genome-level analyses show that the spike protein, which is responsible for receptor binding, has undergone significant Darwinian selection along the branches related to 2019-nCoV and SARS-CoV. Further examination shows an unusually high proportion of evolutionary convergent amino acid sites in the receptor binding domain (RBD) of the spike protein between COVID-19 and SARS-related CoV clades, leading to the phylogenetic uniting of their RBD protein sequences. In addition to the spike protein, we also find the evolutionary convergence of its partner protein, ORF3a, suggesting their possible co-evolutionary convergence. Our results demonstrate a strong adaptive evolutionary convergence between COVID-19 and SARS-related CoV, possibly facilitating their adaptation to similar or identical receptors. Finally, it should be noted that many observed bat SARS-like CoVs that have an evolutionary convergent RBD sequence with 2019-nCoV and SARS-CoV may be pre-adapted to human host receptor ACE2, and hence would be potential new coronavirus sources to infect humans in the future.


title: The important role of polysaccharides from a traditional Chinese medicine-Lung Cleansing and Detoxifying Decoction against the COVID-19 pandemic

text: Abstract The new coronavirus pneumonia, named COVID-19 by the World Health Organization, has become a pandemic. It is highly pathogenic and reproduces quickly. There are currently no specific drugs to prevent the reproduction and spread of COVID-19. Some traditional Chinese medicines, especially the Lung Cleansing and Detoxifying Decoction (Qing Fei Pai Du Tang), have shown therapeutic effects on mild and ordinary COVID-19 patients. Polysaccharides are important ingredients in this decoction. This review summarizes the potential pharmacological activities of polysaccharides isolated by hot water extraction from Lung Cleansing and Detoxifying Decoction, which is consistent with its production method, to provide the theoretical basis for ongoing research on its application.


title: Surgealousy

text: Abstract Answering the call to care for patients with COVID-19 stirs a range of emotions. This perspective explores an individual surgical resident’s early experience in the coronavirus pandemic.


title: Coronavirus (JHM) Replication within the Retina: Analysis of Cell Tropism in Mouse Retinal Cell Cultures

text: Abstract The murine coronavirus, mouse hepatitis virus, JHM strain, induces a retinal degenerative disease in adult BALB/c mice. Coronavirus infections are highly species specific with virus exhibiting a strong tissue and cell specificity. In this report we evaluated the cellular basis of JHM virus retinal tropism. Retinal cultures and retinal pigment epithelial (RPE)-retinal mixed cell cultures were prepared from eyes obtained from Balb/c mice. The ability of JHM virus to infect and replicate in these retinal cultures was evaluated by light microscopy, immunofluorescent staining, electron microscopy, and virus isolation. Cytopathology was not observed and virus could not be detected in supernatant fluid in retinal cultures. However, low levels of infectious virus could be detected within the cells for the first 4 days. This observation suggested that cell-to-cell interactions may be critical since virus particles and virus antigens can be seen in vivo within the neural retina and the RPE. In contrast to the retinal cultures, retinal-RPE mixed cultures were supportive to JHM virus replication. Syncytial cytopathology was observed for the first 4 days and virus was isolated from supernatant fluids. By electron microscopy, virus was found intracellularly within vacuoles and extracellularly at the plasma membrane. After Day 4, a persistent virus infection was established in which cells produced virus for 5 weeks without cytopathic effects or cell death. Double-labeling immunofluorescent studies of retinal-RPE mixed cultures showed that the virus antigen was co-expressed with a Muller cell marker, glutamine synthetase. This cell is the most prominent glial element in the retina. These studies demonstrate that JHM virus is capable of establishing a persistent virus infection in mixed retinal (Muller)-RPE cell cultures. Moreover, these data suggest that cell-to-cell interactions influence the establishment of coronavirus infections in the retina.


title: Efficacy and immunogenicity of recombinant swinepox virus expressing the truncated S protein of a novel isolate of porcine epidemic diarrhea virus

text: Porcine epidemic diarrhea virus (PEDV) causes significant loss to the swine industry. The emergence of novel PEDV strains in recent years has decreased the effectiveness of PEDV vaccines. We have developed a live recombinant vaccine, a swinepox virus vector that expresses a truncated S protein (rSPV-St) from a recent PEDV strain, SQ2014, and evaluated its immunogenicity and effectiveness in a swine model. Vaccination of swine with rSPV-St elicited a robust antibody response specific for the homologous PEDV SQ2014. Serum IgA titers in rSPV-St-vaccinated animals were significantly higher than in those immunized with inactivated vaccines. The effectiveness of antibodies induced by the rSPV-St vaccine in protection against PEDV was tested in a passive-transfer model in which piglets were challenged with the homologous virus SQ2014 and the heterologous strain CV777. When challenged with the homologous virus, sera from rSPV-St vaccination provided complete protection. However, sera from rSPV-St vaccination did not provide any protection against the heterologous virus challenge. Amino acid sequence differences in the S proteins of the two viruses were identified within neutralizing epitopes, which might have contributed to the divergent clinical results. Our data suggest that rSPV-St is potentially an effective vaccine against infection with emerging PEDV strains.


title: A heterologous ‘prime‐boost’ anti‐PEDV immunization for pregnant sows protects neonatal piglets through lactogenic immunity against PEDV

text: ABSTRACT: Porcine epidemic diarrhoea virus (PEDV) causes severe diarrhoea in neonatal suckling piglets with a high mortality. Maternal vaccines that can induce lactogenic immunity to protect suckling piglets via colostrums and milk are pivotal for the prevention and control of PEDV infection in neonatal suckling piglets. In this study, a group of pregnant sows were first orally immunized with coated PEDV‐loaded microspheres and boosted with killed PEDV vaccines (heterologous prime‐boost). It has been detected that the levels of PEDV‐specific antibodies (IgG and IgA) in their sera and milks were higher than other negative groups (P < 0·001 or P < 0·05). Furthermore, it has been proved by the neutralization assay that the induced antibodies could significantly inhibit virus infection as compared to other negative groups (P < 0·01 or P < 0·05). Importantly, after PEDV challenge, more than 90% of the suckling piglets delivered by the sows in the heterologous prime‐boost group were completely protected. Overall, the results show that ‘heterologous prime‐boost’ form is an efficient and effective way to provide protection for suckling piglets against PEDV through lactogenic immunity. SIGNIFICANCE AND IMPACT OF THE STUDY: As a widespread swine pathogen, PEDV affects the swine industry enormously. It causes enteritis in swine of all ages and is often fatal in neonatal piglets. Our data show that pregnant sows were immunized with ‘coated PEDV‐loaded microspheres + killed PEDV vaccines’ (heterologous prime‐boost immunization) could protect more than 90% suckling piglets delivered by the sows against the virus. These findings provide a new model of developing safe and effective immunizations for newborn animals against established and emerging enteric infections.


title: Security Analysis of Drones Systems: Attacks, Limitations, and Recommendations

text: Abstract Recently, the world witnessed a significant increase in the number of used drones, with a global and continuous rise in the demand for their multi-purpose applications. The pervasive aspect of these drones is due to their ability to answer people’s needs. Drones are providing users with a bird’s eye that can be activated and used almost anywhere and at any time. However, recently, the malicious use of drones began to emerge among criminals and cyber-criminals alike. The probability and frequency of these attacks are both high and their impact can be very dangerous with devastating effects. Therefore, the need for detective, protective and preventive counter-measures is highly required. The aim of this survey is to investigate the emerging threats of using drones in cyber-attacks, along the countermeasures to thwart these attacks. The different uses of drones for malicious purposes are also reviewed, along the possible detection methods. As such, this paper analyzes the exploitation of drones vulnerabilities within communication links, as well as smart devices and hardware, including smart-phones and tablets. Moreover, this paper presents a detailed review on the drone/Unmanned Aerial Vehicle (UAV) usage in multiple domains (i.e civilian, military, terrorism, etc.) and for different purposes. A realistic attack scenario is also presented, which details how the authors performed a simulated attack on a given drone following the hacking cycle. This review would greatly help ethical hackers to understand the existing vulnerabilities of UAVs in both military and civilian domains. Moreover, it allows them to adopt and come up with new techniques and technologies for enhanced UAV attack detection and protection. As a result, various civilian and military anti-drones/UAVs (detective and preventive) countermeasures will be reviewed.


title: Priapism in a castrated cat associated with feline infectious peritonitis

text: This report describes a case of feline infectious peritonitis (FIP) in a castrated cat which first presented with the unusual sign of priapism. Laboratory examinations showed increased serum protein content and decreased albumin/globulin ratio. Serum electrophoresis revealed increased α2- and γ-globulin content. One month after the first examination, the cat died. At necropsy, histopathological evaluation of organs showed inflammatory granulomatous lesions compatible with non-effusive FIP and coronavirus-specific polymerase chain reaction confirmed the diagnosis. FIP antigen was demonstrated immunohistochemically in penile tissue.


title: Insulin Degrading Enzyme Induces a Conformational Change in Varicella-Zoster Virus gE, and Enhances Virus Infectivity and Stability

text: Varicella-zoster virus (VZV) glycoprotein E (gE) is essential for virus infectivity and binds to a cellular receptor, insulin-degrading enzyme (IDE), through its unique amino terminal extracellular domain. Previous work has shown IDE plays an important role in VZV infection and virus cell-to-cell spread, which is the sole route for VZV spread in vitro. Here we report that a recombinant soluble IDE (rIDE) enhances VZV infectivity at an early step of infection associated with an increase in virus internalization, and increases cell-to-cell spread. VZV mutants lacking the IDE binding domain of gE were impaired for syncytia formation and membrane fusion. Pre-treatment of cell-free VZV with rIDE markedly enhanced the stability of the virus over a range of conditions. rIDE interacted with gE to elicit a conformational change in gE and rendered it more susceptible to proteolysis. Co-incubation of rIDE with gE modified the size of gE. We propose that the conformational change in gE elicited by IDE enhances infectivity and stability of the virus and leads to increased fusogenicity during VZV infection. The ability of rIDE to enhance infectivity of cell-free VZV over a wide range of incubation times and temperatures suggests that rIDE may be useful for increasing the stability of varicella or zoster vaccines.


title: Pathogenetic determinants in Kawasaki disease: the haematological point of view

text: Kawasaki disease is a multisystemic vasculitis that can result in coronary artery lesions. It predominantly affects young children and is characterized by prolonged fever, diffuse mucosal inflammation, indurative oedema of the hands and feet, a polymorphous skin rash and non‐suppurative lymphadenopathy. Coronary artery involvement is the most important complication of Kawasaki disease and may cause significant coronary stenosis resulting in ischemic heart disease. The introduction of intravenous immunoglobulin decreases the incidence of coronary artery lesions to less than 5%. The etiopathogenesis of this disease remains unclear. Several lines of evidence suggest that an interplay between a microbial infection and a genetic predisposition could take place in the development of the disease. In this review, we summarize the state of the art of pathogenetic mechanisms of Kawasaki disease underscoring the relevance of haematological features as a novel field of investigation.


title: Inactivation of three emerging viruses – severe acute respiratory syndrome coronavirus, Crimean–Congo haemorrhagic fever virus and Nipah virus – in platelet concentrates by ultraviolet C light and in plasma by methylene blue plus visible light

text: BACKGROUND: Emerging viruses like severe acute respiratory syndrome coronavirus (SARS‐CoV), Crimean–Congo haemorrhagic fever virus (CCHFV) and Nipah virus (NiV) have been identified to pose a potential threat to transfusion safety. In this study, the ability of the THERAFLEX UV‐Platelets and THERAFLEX MB‐Plasma pathogen inactivation systems to inactivate these viruses in platelet concentrates and plasma, respectively, was investigated. MATERIALS AND METHODS: Blood products were spiked with SARS‐CoV, CCHFV or NiV, and then treated with increasing doses of UVC light (THERAFLEX UV‐Platelets) or with methylene blue (MB) plus increasing doses of visible light (MB/light; THERAFLEX MB‐Plasma). Samples were taken before and after treatment with each illumination dose and tested for residual infectivity. RESULTS: Treatment with half to three‐fourths of the full UVC dose (0·2 J/cm(2)) reduced the infectivity of SARS‐CoV (≥3·4 log), CCHFV (≥2·2 log) and NiV (≥4·3 log) to the limit of detection (LOD) in platelet concentrates, and treatment with MB and a fourth of the full light dose (120 J/cm(2)) decreased that of SARS‐CoV (≥3·1 log), CCHFV (≥3·2 log) and NiV (≥2·7 log) to the LOD in plasma. CONCLUSION: Our study demonstrates that both THERAFLEX UV‐Platelets (UVC) and THERAFLEX MB‐Plasma (MB/light) effectively reduce the infectivity of SARS‐CoV, CCHFV and NiV in platelet concentrates and plasma, respectively.


A Dermatologist's Perspective of the COVID‐19 Outbreak


title: Equitably Sharing the Benefits and Burdens of Research: Covid‐19 Raises the Stakes

text: One of the central principles of research ethics is that the benefits and burdens of research with human participants should be equitably distributed. This principle has important implications for where research will be conducted, how participants will be recruited, what questions will be investigated, and who will control the distribution of any innovations that result. In the context of Covid‐19, key issues include providing support to clinical trials in low‐ and middle‐income countries, without taking needed resources away from other critical clinical and public health needs; designing recruitment strategies likely to generate sufficient enrollment from groups that have been disproportionately burdened by the virus, such as African Americans; supporting studies designed to improve outcomes in high‐risk environments, such as nursing homes and group homes for the developmentally disabled; and ensuring that the medical products resulting from research are made available throughout the world at an affordable price. If clinical trials are not designed with equity considerations consciously in mind, the response to the pandemic may further exacerbate disparities in health status between population groups.


title: Geldanamycin, a ligand of heat shock protein 90, inhibits herpes simplex virus type 2 replication both in vitro and in vivo

text: Previously, we discovered geldanamycin, a ligand of heat shock protein 90, effectively inhibited herpes simplex virus type 1 replication in vitro and in vivo (mouse encephalitis model). In this study, we demonstrate that geldanamycin has very strong activities against herpes simplex virus type 2 in vitro and in vivo (mouse vagina model). In mouse vagina model, administration of geldanamycin suspension to vagina after virus infection protected the infected mice from death and increased the average survival days in a dose-dependent manner. Geldanamycin also significantly reduced virus shedding from mouse vagina. All geldanamycin-treated groups were statistically significant when compared with the infected control group. The high-dose group of geldanamycin (5.72 mg kg(−1)) was better than acyclovir group (2.86 mg kg(−1)). All geldanamycin vaginal administration mock-infected groups did not show significant body weight loss. Although geldanamycin has strong antiviral activities against various DNA and RNA viruses, geldanamycin is not suitable for systemic administration because of its high toxicity. We consider that geldanamycin is a candidate of topical usage for the treatment of herpes simplex virus type infections. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ja.2012.67) contains supplementary material, which is available to authorized users.


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title: Electronic Health Information Systems to Improve Disease Diagnosis and Management at Point-of-Care in Low and Middle Income Countries: A Narrative Review

text: The purpose of an electronic health information system (EHIS) is to support health care workers in providing health care services to an individual client and to enable data exchange among service providers. The demand to explore the use of EHIS for diagnosis and management of communicable and non-communicable diseases has increased dramatically due to the volume of patient data and the need to retain patients in care. In addition, the advent of Coronavirus disease 2019 (COVID-19) pandemic in high disease burdened low and middle income countries (LMICs) has increased the need for robust EHIS to enable efficient surveillance of the pandemic. EHIS has potential to enable efficient delivery of disease diagnostics services at point-of-care (POC) and reduce medical errors. This review provides an overview of literature on EHIS’s with a focus on describing the key components of EHIS and presenting evidence on enablers and barriers to implementation of EHISs in LMICs. With guidance from the presented evidence, we proposed EHIS key stakeholders’ roles and responsibilities to ensure efficient utility of EHIS for disease diagnosis and management at POC in LMICs.


docid: vfrtzppb

title: Diagnostic utility of additional whole-chest CT as part of an acute abdominal pain CT imaging pathway during the COVID-19 pandemic

text: Abstract Aim To evaluate the diagnostic utility of additional whole-chest computed tomography (CT) in identifying otherwise unheralded COVID-19 lung disease as part of an acute abdominal pain CT imaging pathway in response to the COVID-19 pandemic. MATERIALS AND METHODS Consecutive patients (n=172) who underwent additional whole-chest CT via a COVID-19 acute abdominal pain CT imaging pathway between 27 March and 3 May 2020 were evaluated in this retrospective single-centre study. Chest CT examinations were graded as non-COVID-19, indeterminate for, or classic/probable for COVID-19. CT examinations in the latter two categories were further divided into one of three anatomical distributions (lung base, limited chest [below carina], whole chest [above carina]) based on location of findings. Reverse transcriptase-polymerase chain reaction (RT-PCR) results and clinical features of COVID-19 were assessed to determine if COVID-19 was clinically suspected at the time of CT referral. RESULTS Twenty-seven of the 172 (15.7%) patients had CT features potentially indicative of COVID-19 pneumonia, 6/27 (3.5%) demonstrating a classic/probable pattern and 21/27 (12.2%) demonstrating an indeterminate pattern. After correlation with clinical features and RT-PCR 8/172 (4.7%) were defined as COVID-19 positive, of which only 1/172 (0.6%) was clinically unsuspected of COVID-19 at the time of CT referral. All COVID-19 positive cases could be identified on review of the lung base alone. CONCLUSION Whole-chest CT as part of an acute abdominal pain CT imaging pathway has a very low diagnostic yield for the present cohort of patients. All COVID-19-positive patients in the present cohort were identified on review of the lung bases on the abdominal CT and this offers an alternative imaging approach in this patient group.


Conference report: the 5th Asia Pacific Protein Association Conference joint meeting with the 12th International Symposium of the Protein Society of Thailand


title: Interferon and cytokine responses to SARS-coronavirus infection

text: Abstract The sudden emergence of severe acute respiratory syndrome (SARS) has boosted research on innate immune responses to coronaviruses. It is now well established that the causative agent, a newly identified coronavirus termed SARS-CoV, employs multiple passive and active mechanisms to avoid induction of the antiviral type I interferons in tissue cells. By contrast, chemokines such as IP-10 or IL-8 are strongly upregulated. The imbalance in the IFN response is thought to contribute to the establishment of viremia early in infection, whereas the production of chemokines by infected organs may be responsible for (i) massive immune cell infiltrations found in the lungs of SARS victims, and (ii) the dysregulation of adaptive immunity. Here, we will review the most recent findings on the interaction of SARS-CoV and related Coronaviridae members with the type I interferon and cytokine responses and discuss implications for pathogenesis and therapy.


title: Second-Generation Sequencing with Deep Reinforcement Learning for Lung Infection Detection

text: Recently, deep reinforcement learning, associated with medical big data generated and collected from medical Internet of Things, is prospective for computer-aided diagnosis and therapy. In this paper, we focus on the application value of the second-generation sequencing technology in the diagnosis and treatment of pulmonary infectious diseases with the aid of the deep reinforcement learning. Specifically, the rapid, comprehensive, and accurate identification of pathogens is a prerequisite for clinicians to choose timely and targeted treatment. Thus, in this work, we present representative deep reinforcement learning methods that are potential to identify pathogens for lung infection treatment. After that, current status of pathogenic diagnosis of pulmonary infectious diseases and their main characteristics are summarized. Furthermore, we analyze the common types of second-generation sequencing technology, which can be used to diagnose lung infection as well. Finally, we point out the challenges and possible future research directions in integrating deep reinforcement learning with second-generation sequencing technology to diagnose and treat lung infection, which is prospective to accelerate the evolution of smart healthcare with medical Internet of Things and big data.


title: COVID‐19 polyradiculitis in 24 patients without SARS‐CoV‐2 in the cerebro‐spinal fluid

text: OBJECTIVES to summarise and discuss current knowledge about COVID-19-associated Guillain-Barre syndrome (GBS). METHOD literature review RESULTS: altogether 18 articles were found, which reported 23 patients with COVID-19-associated GBS. A further patient came to our attention by personal communication. Among these 24 included patients age ranged from 20 to 76y. There was male preponderance. Fourteen patients presented with acute inflammatory demyelinating polyneuropathy (AIDP), 4 with acute motor axonal neuropathy (AMAN), 3 with Miller-Fisher syndrome (MFS), and 2 with acute motor and sensory axonal neuropathy (AMSAN). In one patient the subtype was not specified. The cerebrospinal fluid (CSF) was tested for SARS-CoV-2 in 15 patients but was negative for the virus in all of them. Seven patients required artificial ventilation. Twenty-one patients received intravenous immunoglobulines (IVIG). Thirteen patients recovered, 6 did not, and 2 patients died. CONCLUSIONS SARS-CoV-2 can cause GBS. SARS-CoV-2-associated GBS occurs in the absence of the virus in the CSF. Clinical presentation, course, response to treatment, and outcome do not vary between SARS-CoV-2-associated GBS and GBS due to other triggers. This article is protected by copyright. All rights reserved.


title: Coronaviruses and Central Nervous System Manifestations

text: SARS-CoV-2 is a highly pathogenic coronavirus that has caused an ongoing worldwide pandemic. Emerging in Wuhan, China in December 2019, the virus has spread rapidly around the world. Corona virus disease 2019 (COVID-19), which is caused by SARS-CoV-2, has resulted in significant morbidity and mortality. The most prominent symptoms of SARS-CoV-2 infection are respiratory. However, accumulating evidence highlights involvement of the central nervous system (CNS). This includes headache, anosmia, meningoencephalitis, acute ischemic stroke, and several presumably post/para-infectious syndromes and altered mental status not explained by respiratory etiologies. Interestingly, previous studies in animal models emphasized the neurotropism of coronaviruses; thus, these CNS manifestations of COVID-19 are not surprising. This minireview scans the literature regarding the involvement of the CNS in coronavirus infections in general, and in regard to the recent SARS-CoV-2, specifically.


Anesthesia, ethics, and severe acute respiratory syndrome


title: Molecular detection and genotypic characterization of Toxoplasma gondii infection in bats in four provinces of China

text: BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite that infects a wide variety of warm-blooded hosts, including humans. Limited information about T. gondii infection in bats is available in China. The objective of the present study was to determine prevalence and genetic characterization of T. gondii infection in bats in Jilin, Liaoning, Jiangxi and Guangdong provinces, China. METHODS: During May 2005 to August 2013, bats were sampled from Jilin, Liaoning, Jiangxi, and Guangdong provinces, China, and liver tissues were collected for the detection of T. gondii by a nested PCR targeting the B1 gene. The positive samples were genotyped at 11 genetic markers (SAG1, 5′-and 3′-SAG2, alternative SAG2, SAG3, BTUB, GRA6, L358, PK1, c22-8, c29-2, and Apico) using multilocus polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: A total of 626 bats representing 10 species were examined for T. gondii infection, 38 (6.1%) were tested positive with by PCR, 8 positive DNA samples were completely genotyped, of which 3 samples (2 from Cynopterus sphinx, and 1 from Murina leucogaster) represented ToxoDB#10, and 5 samples (2 from Murina leucogaster, 2 from Myotis chinensis, and 1 from Rhinolophus ferrumequinum) belonged to ToxoDB#9 (http://toxodb.org/toxo/). CONCLUSIONS: The present study revealed an overall T. gondii prevalence of 6.1% in bats from Jilin, Liaoning, Jiangxi and Guangdong provinces in China, and reported two T. gondii genotypes (ToxoDB#9 and #10) having a wide geographical distribution in China. These results provide new genetic information about T. gondii infection in bats, and have implications for better understanding of the genetic diversity of T. gondii in China and elsewhere.