title: Target-Dependent Enrichment of Virions Determines the Reduction of High-Throughput Sequencing in Virus Discovery

text: Viral infections cause many different diseases stemming both from well-characterized viral pathogens but also from emerging viruses, and the search for novel viruses continues to be of great importance. High-throughput sequencing is an important technology for this purpose. However, viral nucleic acids often constitute a minute proportion of the total genetic material in a sample from infected tissue. Techniques to enrich viral targets in high-throughput sequencing have been reported, but the sensitivity of such methods is not well established. This study compares different library preparation techniques targeting both DNA and RNA with and without virion enrichment. By optimizing the selection of intact virus particles, both by physical and enzymatic approaches, we assessed the effectiveness of the specific enrichment of viral sequences as compared to non-enriched sample preparations by selectively looking for and counting read sequences obtained from shotgun sequencing. Using shotgun sequencing of total DNA or RNA, viral targets were detected at concentrations corresponding to the predicted level, providing a foundation for estimating the effectiveness of virion enrichment. Virion enrichment typically produced a 1000-fold increase in the proportion of DNA virus sequences. For RNA virions the gain was less pronounced with a maximum 13-fold increase. This enrichment varied between the different sample concentrations, with no clear trend. Despite that less sequencing was required to identify target sequences, it was not evident from our data that a lower detection level was achieved by virion enrichment compared to shotgun sequencing.


title: Ovomucin – a glycoprotein with promising potential

text: Ovomucin, accounting for ∼3.5% of total egg white protein, is responsible for the thick gel characteristics of liquid egg white. Besides its excellent foaming and emulsion capacities, it possesses anti-viral, anti-bacterial, anti-tumor and other bioactivities. This paper reviews compositional, structural, physicochemical, functional and biological properties of ovomucin, as well as development of methods of extraction. As one of the least defined proteins in egg white, further study is required to characterize the structure and to explore its full potential in new applications as functional foods and nutraceuticals.


title: Efficacy and safety of a multiherbal formula with vitamin C and zinc (Immumax) in the management of the common cold

text: OBJECTIVE: To study the potential efficacy and tolerability of a natural multiherbal formula (Immumax) containing Echinacea extract 120 mg, garlic powder 100 mg, Nigella sativa oil 200 mg, and Panax ginseng extract 50 mg plus vitamin C 50 mg and elemental zinc 7.5 mg in the treatment of patients suffering from the common cold. DESIGN AND SETTING: The study was conducted in a prospective, double-blind, randomized, controlled study design in an outpatient setting. PATIENTS AND METHODS: Sixty-two eligible patients with symptoms of the common cold were randomized to either Immumax or placebo treatment groups for the duration of their symptoms or a maximum of 14 days. Resolution rates were estimated using Kaplan–Meier analysis, and resolution profiles were compared between groups using the log-rank test. The mean percentage change in total symptom severity scores at days 4 and 8 from baseline were compared between the two groups by one-way analysis of variance (ANOVA). RESULTS: The median (interquartile range) time to resolution of all symptoms was 8 (5–9) days in the placebo group and 4 (3–6) days in the Immumax group. The results of the log-rank test indicate that symptoms resolved significantly faster in the Immumax group than in the placebo group (P < 0.001). The mean percentage reduction in total symptom severity scores from baseline at days 4 and 8 was significantly greater in the Immumax group than in the placebo group by one-way ANOVA (P < 0.01). CONCLUSION: We can conclude from our study that Immumax is helpful in reducing the duration and severity of common cold symptoms.


title: Current situation in the development of a preventive HIV vaccine

text: The uncontrolled progression of the aids epidemic has made the development of an efficacious human immunodeficiency virus (HIV) vaccine a major objective of scientific research. No effective preventive vaccine against HIV is currently available and sterilizing immunity has not yet been achieved in animal models. This review analyses the major challenges in developing an aids vaccine, in particular the mechanisms involved in viral escape from the immune response, and summarizes the results obtained with the different prototypes of therapeutic and preventive vaccines. Finally, social, economic and healthcare aspects of research into HIV vaccines and current controversies regarding the development of clinical trials are discussed.


title: Interacciones medicamentosas potenciales en pacientes COVID 19 en tratamiento con lopinavir/ritonavir

text: Resumen Objetivos: Determinar la prevalencia de interacciones potenciales en pacientes COVID19 en tratamiento con lopinavir/ritonavir (LPV/r). El objetivo secundario fue elaborar recomendaciones e identificar los factores de riesgo asociados a presentar interacciones potenciales con LPV/r. Sujetos y Métodos: Estudio transversal y multicéntrico con la participación 2 hospitales. Se incluyeron pacientes COVID 19 mayores de 18 años, con ingreso hospitalario y en tratamiento con LPV/r. Se realizó un cribado de las interacciones potenciales relacionadas con LPV/r y la medicación domiciliaria y hospitalaria. Se utilizó como base de datos de consulta Lexicomp® (Uptodate), HIV-drug interacctions y COVID-drug interacctions. Resultados: Se incluyeron 361 pacientes con una media de edad de 62,77 ± 14,64 años, donde el 59,6 % (n=215) fueron hombres. El 62,3% (n=225) tuvieron 1 o más interacciones potenciales y el 26, 87% (n=97) 2 o más. Las variables independientes asociadas a presentar ≥ 1 interacciones potenciales fueron la edad (> 65) (OR 1,95; IC 95% 1,06-3,59; P=0,033), el ingreso en UCI (OR 9,22; IC 95% 1,98-42,93; P=0,005), la patología previa respiratoria (OR 2,90; IC 95% 1,15-7,36; P=0,024), psiquiátrica (OR 4,14; IC 95% 1,36-12,61; P=0,013), la dislipemia (OR 3,21; IC 95% 1.63-6,35; P=0,001) y el número de fármacos prescrito (OR 4,33; IC 95% 2,40-7,81; P=0,000). Conclusión: La prevalencia de interacciones potenciales en paciente COVD 19 en tratamiento con LPV/r es elevada, comportándose como factores de riesgo asociados la edad (>65), el ingreso en UCI, la patología previa respiratoria, psiquiátrica y la dislipemia y el número de fármacos prescritos. Abstract Objectives: To determine the prevalence of potential interactions in COVID19 patients receiving lopinavir/ritonavir (LPV/r). The secondary objective was to develop recommendations and identify the risk factors associated with presenting potential interactions with LPV/r. Subjects and Methods: Cross-sectional and multicenter study with the participation of 2 hospitals. COVID 19 patients over 18 years of age, admitted to hospital and under treatment with LPV/r were included. A screening of potential interactions related to LPV/r and home and hospital medication was carried out. Lexicomp® (Uptodate), HIV-drug interactions and COVID-drug interactions were used as the query database. Results: 361 patients with a mean age of 62.77 ± 14.64 years were included, where 59.6% (n = 215) were men. 62.3% (n = 225) had 1 or more potential interactions and 26, 87% (n = 97) 2 or more. The independent variables associated with presenting ≥1 potential interactions were age (> 65) (OR 1.95; 95% CI 1.06-3.59, P = 0.033), ICU admission (OR 9.22; CI 95% 1.98-42.93; P = 0.005), previous respiratory pathology (OR 2.90; 95% CI 1.15-7.36; P = 0.024), psychiatric (OR 4.14; 95 CI % 1.36-12.61; P = 0.013), dyslipidemia (OR 3.21; 95% CI 1.63-6.35; P = 0.001) and the number of drugs prescribed (OR 4.33; 95% CI 2.40-7.81; P = 0.000). Conclusion: The prevalence of potential interactions in COVD 19 patient undergoing treatment with LPV/r is high, with age (> 65), ICU admission, previous respiratory and psychiatric pathology, dyslipidemia and the number of prescribed drugs acting as risk factors.


title: A 60-year review on the changing epidemiology of measles in capital Beijing, China, 1951-2011

text: BACKGROUND: China pledged to join the global effort to eliminate measles by 2012. To improve measles control strategy, the epidemic trend and population immunity of measles were investigated in 1951–2011 in Beijing. METHODS: The changing trend of measles since 1951 was described based on measles surveillance data from Beijing Centre of Disease Control and Prevention (CDC). The measles vaccination coverage and antibody level were assessed by routinely reported measles vaccination data and twenty-one sero-epidemiological surveys. RESULTS: The incidence of measles has decreased significantly from 593.5/100,000 in 1951 (peaked at 2721.0/100,000 in 1955), to 0.5/100,000 in 2011 due to increasing vaccination coverage of 95%-99%. Incidence rebounded from 6.6/100,000 to 24.5/100,000 since 2005 and decreased after measles vaccine (MV) supplementary immunization activities (SIAs) in 2010. Measles antibody positive rate was 85%-95% in most of years since 1981. High-risk districts were spotted in Chaoyang, Fengtai and Changping districts in recent 15 years. Age-specific incidence and proportion of measles varied over time. The most affected population were younger children of 1–4 years before 1978, older children of 5–14 years in 1978–1996, infant of <1 years and adults of ≥15 years in period of aim to measles elimination. CONCLUSION: Strategies at different stages had a prevailing effect on the epidemic dynamics of measles in recent 60 years in Beijing. It will be essential to validate reported vaccination coverage, improve vaccination coverage in adults and strengthen measles surveillance in the anticipated elimination campaign for measles.


Modelado estadístico y matemático en la epidemía del coronavirus: Algunas consideraciones para minimizar los sesgos en los resultados


title: Interleukin-2 signalling is modulated by a labile disulfide bond in the CD132 chain of its receptor

text: Certain disulfide bonds present in leucocyte membrane proteins are labile and can be reduced in inflammation. This can cause structural changes that result in downstream functional effects, for example, in integrin activation. Recent studies have shown that a wide range of membrane proteins have labile disulfide bonds including CD132, the common gamma chain of the receptors for several cytokines including interleukin-2 and interleukin-4 (IL-2 and IL-4). The Cys(183)–Cys(232) disulfide bond in mouse CD132 is susceptible to reduction by enzymes such as thioredoxin (TRX), gamma interferon-inducible lysosomal thiolreductase and protein disulfide isomerase, which are commonly secreted during immune activation. The Cys(183)–Cys(232) disulfide bond is also reduced in an in vivo lipopolysaccharide (LPS)-induced acute model of inflammation. Conditions that lead to the reduction of the Cys(183)–Cys(232) disulfide bond in CD132 inhibit proliferation of an IL-2-dependent T cell clone and concomitant inhibition of the STAT-5 signalling pathway. The same reducing conditions had no effect on the proliferation of an IL-2-independent T cell clone, nor did they reduce disulfide bonds in IL-2 itself. We postulate that reduction of the Cys(183)–Cys(232) disulfide in CD132 inhibits IL-2 binding to the receptor complex. Published data show that the Cys(183)–Cys(232) disulfide bond is exposed at the surface of CD132 and in close contact with IL-2 and IL-4 in their respective receptor complexes. In addition, mutants in these Cys residues in human CD132 lead to immunodeficiency and loss of IL-2 binding. These results have wider implications for the regulation of cytokine receptors in general, as their activity can be modulated by a ‘redox regulator’ mechanism caused by the changes in the redox environment that occur during inflammation and activation of the immune system.


title: Chloroquine differentially modulates coronary vasodilation in control and diabetic mice

text: Background and Purpose: Chloroquine is a traditional medicine to treat malaria. There is increasing evidence that chloroquine not only induces phagocytosis but regulates vascular tone. Few reports investigating the effect of chloroquine on vascular responsiveness of coronary arteries have been made. In this study, we examined how chloroquine affected endothelium-dependent relaxation in coronary arteries under normal and diabetic conditions. Experimental Approach: We isolated coronary arteries from mice and examined endothelium-dependent relaxation (EDR). Human coronary endothelial cells and mouse coronary endothelial cells isolated from control and diabetic mouse (TALLYHO/Jng [TH] mice, a spontaneous type 2 diabetic mouse model) were used for the molecular biological or cytosolic NO and Ca2+measurements. Key Results: Chloroquine inhibited endothelium-derived NO-dependent relaxation but had negligible effect on endothelium-derived hyperpolarization (EDH)-dependent relaxation in coronary arteries of control mice. Chloroquine significantly decreased NO production in control human coronary endothelial cells partly by phosphorylating eNOSThr495(an inhibitory phosphorylation site of eNOS) and attenuating the rise of cytosolic Ca2+concentration after stimulation. EDR was significantly inhibited in diabetic mice in comparison to control mice. Interestingly, chloroquine enhanced EDR in diabetic coronary arteries by, specifically, increasing EDH-dependent relaxation due partly to its augmenting effect on gap junction activity in diabetic mouse coronary endothelial cells. Conclusions and Implications: These data indicate that chloroquine affects vascular relaxation differently under normal and diabetic conditions. Therefore, the patients' health condition such as coronary macrovascular or microvascular disease, with or without diabetes, must be taken account into the consideration when selecting chloroquine for the treatment of malaria.


title: Recurrence of positive SARS-CoV-2 RNA in COVID-19: A case report

text: Abstract The ongoing outbreak of COVID-19 that began in Wuhan, China, has constituted a Public Health Emergency of International Concern, with cases confirmed in multiple countries. Currently, patients are the primary source of infection. We report a confirmed case of COVID-19 whose oropharyngeal swab test of SARS-CoV-2 RNA turned positive in convalescence. This case highlights the importance of active surveillance of SARS-CoV-2 RNA for infectivity assessment.


title: Host Biomarkers and Paediatric Infectious Diseases: From Molecular Profiles to Clinical Application

text: Infectious diseases are an important cause of death among children under the age of 5 (Stein et al., 2004). Most of these deaths are caused by preventable or curable infections. Limited access to medical care, antibiotics, and vaccinations remains a major problem in developing countries. But infectious diseases also continue to be an important public health issue in developed countries. With the help of modern technologies, some infections have been effectively controlled; however, new diseases such as SARS and West Nile virus infections are constantly emerging. In addition, other diseases such as malaria, tuberculosis, and bacterial pneumonia are increasingly resistant to antimicrobial treatment.


title: Novel Human Gammapapillomavirus Species in a Nasal Swab

text: A divergent human gammapapillomavirus (γ-HPV) genome in a nasal swab from an elderly Finnish patient with respiratory symptoms was genetically characterized. The L1 gene of HPV-Fin864 shared <70% nucleotide identity to other reported γ-HPV genomes, provisionally qualifying it as a new species in the Gammapapillomavirus genus.


title: T-cell immunosenescence: lessons learned from mouse models of aging

text: It is well established that increasing age is associated with a decreased capacity of the immune system to mediate effective immune responses to vaccination and invading pathogens. Because of the inherent limitations of conducting experiments in humans, much of what we have learned is owed to the utility of experimental mouse models of aging. Recent studies performed in the mouse have demonstrated mechanisms responsible for age-related declines in the function of CD4(+) and CD8(+) cells. This review describes key findings regarding age-related defects in T-cell function and discusses the impact these defects have on vaccine efficacy and immunity.


title: Radiolabeled antiviral drugs and antibodies as virus-specific imaging probes

text: Abstract A number of small-molecule drugs inhibit viral replication by binding directly to virion structural proteins or to the active site of a viral enzyme, or are chemically modified by a viral enzyme before inhibiting a downstream process. Similarly, antibodies used to prevent or treat viral infections attach to epitopes on virions or on viral proteins expressed on the surface of infected cells. Such drugs and antibodies can therefore be thought of as probes for the detection of viral infections, suggesting that they might be used as radiolabeled tracers to visualize sites of viral replication by single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. A current example of this approach is the PET imaging of herpes simplex virus infections, in which the viral thymidine kinase phosphorylates radiolabeled thymidine analogues, trapping them within infected cells. One of many possible future applications might be the use of a radiolabeled hepatitis C protease inhibitor to image infection in animals or humans and provide a quantitative measure of viral burden. This article reviews the basic features of radionuclide imaging and the characteristics of ideal tracer molecules, and discusses how antiviral drugs and antibodies could be evaluated for their suitability as virus-specific imaging probes. The use of labeled drugs as low-dose tracers would provide an alternative application for compounds that have failed to advance to clinical use because of insufficient in vivo potency, an unsuitable pharmacokinetic profile or hepato- or nephrotoxicity.


title: Dopamine D3 receptor-based medication development for the treatment of opioid use disorder: Rationale, progress, and challenges

text: Opioid abuse and related overdose deaths continue to rise in the United States, contributing to the current national opioid crisis. Although several opioid-based pharmacotherapies are available (e.g., methadone, buprenorphine, naloxone), they show limited effectiveness in long-term relapse prevention. In response to the opioid crisis, the National Institute on Drug Abuse proposed a list of pharmacological targets of highest priority for medication development for the treatment of opioid use disorders (OUD). Among these are antagonists of dopamine D3 receptors (D3R). In this review, we first review recent progress in research of the dopamine hypothesis of opioid reward and abuse and then describe the rationale and recent development of D3R ligands for the treatment of OUD. Herein, an emphasis is placed on the effectiveness of newly developed D3R antagonists in the animal models of OUD. These new drug candidates may also potentiate the analgesic effects of clinically used opioids, making them attractive as adjunctive medications for pain management and treatment of OUD.


Surgeons' response to COVID‐19: modified workflow to adapt to the new normal


title: After 2015: infectious diseases in a new era of health and development

text: Running over timescales that span decades or centuries, the epidemiological transition provides the central narrative of global health. In this transition, a reduction in mortality is followed by a reduction in fertility, creating larger, older populations in which the main causes of illness and death are no longer acute infections of children but chronic diseases of adults. Since the year 2000, the Millennium Development Goals (MDGs) have provided a framework for accelerating the decline of infectious diseases, backed by a massive injection of foreign investment to low-income countries. Despite the successes of the MDGs era, the inhabitants of low-income countries still suffer an enormous burden of disease owing to diarrhoea, pneumonia, HIV/AIDS, tuberculosis, malaria and other pathogens. Adding to the predictable burden of endemic disease, the threat of pandemics is ever-present and global. With a view to the future, this review spotlights five aspects of the fight against infection beyond 2015, when the MDGs will be replaced by a new set of goals for poverty reduction and sustainable development. These aspects are: exploiting the biological links between infectious and non-infectious diseases; controlling infections among the new urban majority; enhancing the response to international health threats; expanding childhood immunization programmes to prevent acute and chronic diseases in adults; and working towards universal health coverage. By scanning the wider horizon now, infectious disease specialists have the chance to shape the post-2015 era of health and development.


title: Sustainable management measures for healthcare waste in China

text: Abstract This paper discusses actions aimed at sustainable management of healthcare wastes (HCW) in China, taking into account the current national situation in this field, as well as the requirements deriving from the Stockholm Convention on Persistent Organic Pollutants and the WHO recommendations. By the end of 2005, there were 149 low-standard HCW disposal facilities in operation in China, distributed throughout different areas. According to the National Hazardous Waste and Healthcare Waste Disposal Facility Construction Plan, 331 modern, high-standard, centralized facilities will be built up in China in municipal level cities. Although incineration is still the main technical option for HCW disposal in China, it is expected that, especially for medium and small size facilities, non-incineration technologies will develop quickly and will soon become the main technical option. The basic management needs – both from the point of view of pollution control and final disposal – have been defined, and a system of technical and environmental standards has been formulated and implemented; however, there are still some shortages. This is particularly true when considering the best available techniques and best environmental practices developed under the Stockholm Convention, with which the present technological and managing situations are not completely compliant. In this framework, the lifecycle (from generation to final disposal of wastes) of HCW and holistic approaches (technology verification, facilities operation, environmental supervision, environmental monitoring, training system, financial mechanism, etc.) towards HCW management are the most important criteria for the sustainable and reliable management of HCW in China.


title: Effect of Convalescent Plasma Therapy on Viral Shedding and Survival in COVID-19 Patients

text: Currently, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) has been reported in almost all countries globally, and no effective therapy has been documented for COVID-19 and the role of convalescent plasma therapy is unknown. In current study, 6 COVID-19 subjects with respiratory failure received convalescent plasma at a median of 21.5 days after first detection of viral shedding, all tested negative for SARS-CoV-2 RNA by 3 days after infusion, and 5 died eventually. In conclusion, convalescent plasma treatment can discontinue SARS-CoV-2 shedding but cannot reduce mortality in critically end-stage COVID-19 patients, and treatment should be initiated earlier.


title: Hyponatremia in children with respiratory infections: a cross-sectional analysis of a cohort of 3938 patients

text: Hyponatremia can be a life-threatening illness among hospitalized children. The aims of this study were to evaluate the incidence and risk factors of hyponatremia in 3938 children who were admitted to the Cheil General Hospital and Women’s Health Care Center with respiratory infections. Clinical data were collected, and multiplex RT-PCR analyses were done for various microorganisms. Hyponatremia was observed in 531 (13.5%) patients. The incidence of hyponatremia differed according to the respiratory tract infection (P < 0.0001) and microorganism (P = 0.001). In children with hyponatremia, the age at admission was significantly older (P < 0.0001), male gender was more frequent (P = 0.019), CRP was higher (P < 0.0001), and coinfection with multiple organisms was more common (P = 0.001) than in children without hyponatremia. In multivariate analyses, an older age at admission (P = 0.006), male gender (P = 0.004), and increased CRP (P < 0.0001) were independent risk factors. Sodium levels correlated negatively with WBC (P = 0.037), CRP (P < 0.0001), and number of hospital days (P = 0.020). The AUC values of age (0.586, P < 0.0001), CRP (0.599, P < 0.0001), and blood urea nitrogen (0.559, P < 0.0001) were all significant predictors of hyponatremia. This study is the first to show that the incidence of hyponatremia differs according to infecting microorganism and radiological findings.


title: Biological exacerbation clusters demonstrate asthma and chronic obstructive pulmonary disease overlap with distinct mediator and microbiome profiles

text: BACKGROUND: Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous. OBJECTIVE: We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations. METHODS: Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center. Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation. Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators. Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters. RESULTS: The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology. Three exacerbation biologic clusters were identified. Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria. Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes. Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes. CONCLUSIONS: A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD. The sputum mediator and microbiome profiles were distinct between clusters.


title: The modified NUTRIC score can be used for nutritional risk assessment as well as prognosis prediction in critically ill COVID-19 patients

text: Summary Background and Aims In the newly emerged Coronavirus Disease 2019 (COVID-19) disaster, little is known about the nutritional risks for critically ill patients. It is also unknown whether the modified Nutrition Risk in the Critically ill (mNUTRIC) score is applicable for nutritional risk assessment in intensive care unit (ICU) COVID-19 patients. We set out to investigate the applicability of the mNUTRIC score for assessing nutritional risks and predicting outcomes for these critically ill COVID-19 patients. Methods This retrospective observational study was conducted in three ICUs which had been specially established and equipped for COVID-19 in Wuhan, China. The study population was critically ill COVID-19 patients who had been admitted to these ICUs between January 28 and February 21, 2020. Exclusion criteria were as follows: 1) patients of <18 years; 2) patients who were pregnant; 3) length of ICU stay of <24 hours; 4) insufficient medical information available. Patients’ characteristics and clinical information were obtained from electronic medical and nursing records. The nutritional risk for each patient was assessed at their ICU admission using the mNUTRIC score. A score of ≥5 indicated high nutritional risk. Mortality was calculated according to patients’ outcomes following 28 days of hospitalization in ICU. Results A total of 136 critically ill COVID-19 patients with a median age of 69 years (IQR: 57-77), 86 (63%) males and 50 (37%) females, were included in the study. Based on the mNUTRIC score at ICU admission, a high nutritional risk (≥5 points) was observed in 61% of the critically ill COVID-19 patients, while a low nutritional risk (<5 points) was observed in 39%. The mortality of ICU 28-day was significantly higher in the high nutritional risk group than in the low nutritional risk group (87% vs 49%, P <0.001). Patients in the high nutritional risk group exhibited significantly higher incidences of acute respiratory distress syndrome, acute myocardial injury, secondary infection, shock and use of vasopressors. Additionally, use of a multivariate Cox analysis showed that patients with high nutritional risk had a higher probability of death at ICU 28-day than those with low nutritional risk (adjusted HR =2.01, 95% CI: 1.22-3.32, P =0.006). Conclusions A large proportion of critically ill COVID-19 patients had a high nutritional risk, as revealed by their mNUTRIC score. Patients with high nutritional risk at ICU admission exhibited significantly higher mortality of ICU 28-day, as well as twice the probability of death at ICU 28-day than those with low nutritional risk. Therefore, the mNUTRIC score may be an appropriate tool for nutritional risk assessment and prognosis prediction for critically ill COVID-19 patients.


title: Die virale Gastroenteritis

text: The acute gastroenteritis is a problem not only in developing countries but also in Europe. Rotaviruses cause severe disease in the young infant and noroviruses cause milder disease in all age groups. They are responsible for countless outbreaks in hospitals, nurseries, day care centers, hotels and restaurants. Rehydration of infants and neonates can be challenging, but handling of viral gastroenteritis in general is easy. Outbreak management on the other hand can be laborious and time consuming. This report is an overview on pathogenesis, management and epidemiology of the most important viruses causing acute gastroenteritis.


Clinical research and COVID-19: Science is not an option


title: Novel decoy cellular vaccine strategy utilizing transgenic antigen-expressing cells as immune presenter and adjuvant in vaccine prototype against SARS-CoV-2 virus

text: Abstract A novel approach modifying cells to express viral markers to elicit protective immunity responses (decoy cellular vaccination) in the prevention of COVID-19 disease is currently being explored. Our approach entails utilizing SARS-CoV-2 Spike antigen-expressing, non-replicating cells as carriers and presenters of immunogenic antigens, so called “I-cells”. By using irradiated cells as presenting vehicles of SARS-CoV-2 viral antigens(s) in a cellular context, these presented viral proteins can be recognized by the host immune system, thus, an efficient protective immune response might be elicited. Another advantage of this strategy is that the manufacturing process is scalable and yields uniform cell products allowing for “off-the-shelf” frozen supply availability. To prevent engraftment and proliferation of the cells after administration, the cells will be irradiated post-harvesting abolishing in vivo replication potential. Specifically, immunoreactive Spike-1 proteins from SARS-CoV-2 are expressed on the surface of irradiated target I-cells. Utilizing this innovative strategy, these viral antigen-displaying decoy cells will be developed as a vaccine to protect against COVID-19 disease.


title: Development of a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for the detection of porcine pegivirus

text: Abstract A simple and accurate reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay was developed and evaluated for the detection of porcine pegivirus (PPgV). The specific RT-LAMP primers targeting the conserved regions of NS5A genes were designed and used to detect PPgV. The optimal reaction parameter for RT-LAMP assay was 63℃ for 60 min. The detection limit of the RT-LAMP assay was 10 copies of PPgV genome, which was 100 times more sensitive than that of the conventional RT-PCR and comparable to nested RT-PCR and quantitative RT-PCR (qRT-PCR). There was no cross amplification with other related RNA viruses. In the clinical evaluation, the RT-LAMP assay exhibited a similar sensitivity with nested RT-PCR and qRT-PCR. The results indicated that RT-LAMP assay developed in this study could be a highly specific, sensitive, and cost-effective alternative for a rapid detection of PPgV in field settings.


title: Immune Responses of the Bovine Fetus 1

text: Abstract The bovine fetus is capable of mounting an antibody response when a bacterial antigen (killed Escherichia coli) or viral antigen (live reovirus) is deposited into the amniotic fluid. Time required for the fetus to respond to bacterial antigen given orally (amniotic fluid) is approximately 10 to 14 days and 8 to 10 days for viral antigen. Calves vaccinated prenatally with E. coli from 9 to 102 days before birth and deprived of colostrum survived oral challenge doses of viable E. coli which killed calves not vaccinated prenatally. One mechanism of protection was the local production of antibody in the gastrointestinal mucosa where immunofluo rescent techniques showed immunoglobulins IgG, IgM, and anti-E. coli antibody in the duodenum, jejunum, and ileum as well as in the jejunal lymph node. Prenatal vaccination has been used in the field for prevention of colibacillosis. However, the occurrence of some stillbirths and premature births indicates the need for further research before there can be widespread field application of the technique.


title: Long Distance Reverse-Transcription PCR

text: Polymerase chain reaction (PCR) has been applied to the amplification of long DNA fragments from a variety of sources, including genomic, mitochondrial, and viral DNAs (1-5). We have adapted the concept of long PCR technology to reverse-transcription (RT) PCR (6). Here, we describe the parameters critical in producing RT-PCR products of up to 20 kbp. The nature of RT-PCR requires the synthesis of a cDNA by RT prior to its amplification in the PCR reaction. Thus, we focus on the three steps of RT-PCR: the preparation and requirements of the RNA template, the reverse transcription reaction, and the amplification of the cDNA by PCR.


title: Intracellular Crosslinking of Filoviral Nucleoproteins with Xintrabodies Restricts Viral Packaging

text: Viruses assemble large macromolecular repeat structures that become part of the infectious particles or virions. Ribonucleocapsids (RNCs) of negative strand RNA viruses are a prime example where repetition of nucleoprotein (NP) along the genome creates a core polymeric helical scaffold that accommodates other nucleocapsid proteins including viral polymerase. The RNCs are transported through the cytosol for packaging into virions through association with viral matrix proteins at cell membranes. We hypothesized that RNC would be ideal targets for crosslinkers engineered to promote aberrant protein–protein interactions, thereby blocking their orderly transport and packaging. Previously, we had generated single-domain antibodies (sdAbs) against Filoviruses that have all targeted highly conserved C-terminal regions of NP known to be repetitively exposed along the length of the RNCs of Marburgvirus (MARV) and Ebolavirus (EBOV). Our crosslinker design consisted of dimeric sdAb expressed intracellularly, which we call Xintrabodies (X- for crosslinking). Electron microscopy of purified NP polymers incubated with purified sdAb constructs showed NP aggregation occurred in a genus-specific manner with dimeric and not monomeric sdAb. A virus-like particle (VLP) assay was used for initial evaluation where we found that dimeric sdAb inhibited NP incorporation into VP40-based VLPs whereas monomeric sdAb did not. Inhibition of NP packaging was genus specific. Confocal microscopy revealed dimeric sdAb was diffuse when expressed alone but focused on pools of NP when the two were coexpressed, while monomeric sdAb showed ambivalent partition. Infection of stable Vero cell lines expressing dimeric sdAb specific for either MARV or EBOV NP resulted in smaller plaques and reduced progeny of cognate virus relative to wild-type Vero cells. Though the impact was marginal at later time-points, the collective data suggest that viral replication can be reduced by crosslinking intracellular NP using relatively small amounts of dimeric sdAb to restrict NP packaging. The stoichiometry and ease of application of the approach would likely benefit from transitioning away from intracellular expression of crosslinking sdAb to exogenous delivery of antibody. By retuning sdAb specificity, the approach of crosslinking highly conserved regions of assembly critical proteins may well be applicable to inhibiting replication processes of a broad spectrum of viruses.


title: Molecular mechanisms for thrombosis risk in Black people: a role in excess mortality from COVID‐19

text: We read with interest your recent article by Fogarty et al, in particular their conclusion that differences in thrombotic risk may contribute to ethnic disparities in mortality from Covid-19.(1) This is especially important in the UK, where age-sex adjusted hospital death rates for Covid-19 are 2.17 times higher for people with ethnicity recorded as black compared to those recorded as white, and 1.95 higher for those recorded as Asian.(2) This excess mortality persists after adjustment for deprivation, body mass index (BMI), smoking and comorbidities,(2) and despite correction for region, rural or urban living, deprivation, household composition, socioeconomic status, and health.(3) Similar data from the USA shows that in 14 states, African-Americans represent 33% of hospitalisations for Covid-19, despite only making up 14% of the catchment population.(4) Black ethnicity is a construct incorporating diverse populations of African descent. Studies from several communities labelled as black, in particular African-Americans, imply a common increase in thrombotic risk, which may contribute to unexplained ethnic disparities in the UK and USA in Covid-19.


title: Emerging viral diseases from a vaccinology perspective: preparing for the next pandemic

text: Emerging infectious diseases will continue to threaten public health and are sustained by global commerce, travel and disruption of ecological systems. Most pandemic threats are caused by viruses from either zoonotic sources or vector-borne sources. Developing better ways to anticipate and manage the ongoing microbial challenge will be critical for achieving the United Nations Sustainable Development Goals and, conversely, each such goal will affect the ability to control infectious diseases. Here we discuss how technology can be applied effectively to better prepare for and respond to new viral diseases with a focus on new paradigms for vaccine development.


title: Broad-spectrum activity of 8-chloro-7-deazaguanosine against RNA virus infections in mice and rats

text: Abstract A novel nucleoside analog, 8-chloro-7-deazaguanosine (8-Cl-7-dzGuo), was evaluated for anti-RNA virus activity in rodents in parallel with the related compound 7-deaza-7-thia-8-oxoguanosine (7-dzTOGuo). Half-daily intraperitoneal (i.p.) doses of each substance administered 24 and 18 h prior to i.p. virus challenge protected the majority of mice infected with banzi, encephalomyocarditis, San Angelo, and Semliki Forest viruses at doses of 25, 50 and 100 mg/kg/day. These compounds at 100 mg/kg/day also protected most suckling rats infected intranasally with rat coronavirus. However, no survival benefit was afforded to treated mice infected intranasally with vesicular stomatitis virus. 8-Cl-7-dzguo was orally active against Semliki Forest virus in mice at 200 and 400 mg/kg/day, whereas 7-dzTOGuo is reported to not be effective orally. In uninfected mice, the two compounds induced similar amounts of interferon following i.p. injections. Interferon was induced by oral treatments with 8-Cl-7-dzGuo but not with 7-dzTOGuo. Fifty percent acute lethal doses to uninfected mice treated i.p. in half-daily doses for one day with 7-deazaguanosine (7-dzGuo), 7-dzTOGuo, and 8-Cl-7-dzGuo were 400, 600 and > 1600 (no mortality at this dose) mg/kg/day, respectively. Daily, i.p. treatments for 14 days with these substances (100 mg/kg/day) showed 7-dzGuo as 100% lethal and the other two substances at not toxic. By virtue of reduced toxicity and oral bioavailability, 8-Cl-7-dzGuo appears to have the greatest clinical potential as an interferon-inducing antiviral agent.


title: A COVID-19 pandemic guideline in evidence-based medicine

text: Data sources This review article scrutinised 16 clinical studies (clinical trials and observational studies) concerning coronavirus disease of 2019 (COVID-19). Additionally, 18 guidelines about the COVID-19 were reviewed and the key points were represented in this study. Study selection The review included human trials, in-vitro studies, review articles, and credible news reports about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 complications, treatment guidelines, management strategies, and epidemiological features. There were no exclusion criteria reported in this review and the included information was in English and Chinese languages. Data extraction and synthesis A descriptive review of the literature was conducted, taking a comprehensive approach. The paper consisted of three main parts: introduction, presentation, and management. The introduction part presented basic information about the SARS-CoV-2, its evolution and transmission, and the course of disease. The presentation section introduced the signs and symptoms, diagnosis, high risk groups, and complications of COVID-19. Eventually, some evidence was presented about the prevention, medical management, and measuring responses to the treatments in the management section. Results Based on the results of this study, non-pharmaceutical interventions, including strict social isolation and distancing measures, might reduce the spread of the SARS-CoV-2 by nearly 99.3 percent (reproduction number mitigating from 406 to 2.5 in 30 days). In the supportive management section, monitoring vital signs and neonatal feeding were stated as the most important factors to consider. For symptomatic neonates, medical management and intervention were mentioned as essential. It was claimed that for adults with mild infection, the best option would be home quarantine with further medical monitoring or hospitalisation if required. The following sequence was also suggested as early supportive therapy and monitoring: intravenous fluid administration, oxygen therapy, and application of corticosteroids. Management of critical patients with critical COVID-19 included admission to intensive care unit, use of continuous positive airway pressure and bi-level positive airway pressure in certain circumstances, endotracheal intubation, invasive mechanical ventilation, extracorporeal membrane oxygenation, and fluid resuscitation and vasopressors. Additionally, this study suggested oseltamivir, iopinavir, remdesivir, chloroquine, baricitinib, ruxolitinib, and fedratinib as possible drugs to help manage COVID-19. A soaring c-reactive protein level and decreased albumin content in the blood were reported to be associated with a deteriorating status in COVID-19 patients. To keep the number of exposures to a minimum, two separate viral clearance tests taken at least 24 hours apart, were stated as necessary laboratory results before the discharge of patients with COVID-19. Conclusions The study warns about possible exponential spread of COVID-19 and proposes to adhering to tighter restrictions of social distancing. Besides the clinical guidelines presented within the study, it also encourages further up-to-date and evidence-based management guidelines for patients with COVID-19.


title: IFITM proteins—cellular inhibitors of viral entry

text: Interferon inducible transmembrane (IFITM) proteins are a recently discovered family of cellular anti-viral proteins that restrict the replication of a number of enveloped and non-enveloped viruses. IFITM proteins are located in the plasma membrane and endosomal membranes, the main portals of entry for many viruses. Biochemical and membrane fusion studies suggest IFITM proteins have the ability to inhibit viral entry, possibly by modulating the fluidity of cellular membranes. Here we discuss the IFITM proteins, recent work on their mode of action, and future directions for research.


title: Ethnic Disparities in Hospitalization for COVID-19: a Community-Based Cohort Study in the UK

text: IMPORTANCE: Differentials in COVID-19 incidence, hospitalization and mortality according to ethnicity are being reported but their origin is uncertain. OBJECTIVE: We aimed to explain any ethnic differentials in COVID-19 hospitalization based on socioeconomic, lifestyle, mental and physical health factors. DESIGN: Prospective cohort study with national registry linkage to hospitalisation for COVID-19. SETTING: Community-dwelling. PARTICIPANTS: 340,966 men and women (mean age 56.2 (SD=8.1) years; 54.3% women) residing in England from the UK Biobank study. EXPOSURES: Ethnicity classified as White, Black, Asian, and Others. MAIN OUTCOME(S) AND MEASURE(S): Cases of COVID-19 serious enough to warrant a hospital admission in England from 16-March-2020 to 26-April-2020. RESULTS: There were 640 COVID-19 cases (571/324,306 White, 31/4,485 Black, 21/5,732 Asian, 17/5,803 Other). Compared to the White study members and after adjusting for age and sex, Black individuals had over a 4-fold increased risk of being hospitalised (odds ratio; 95% confidence interval: =4.32; 3.00-6.23), and there was a doubling of risk in the Asian group (2.12; 1.37, 3.28) and the ‘other’ non-white group (1.84; 1.13, 2.99). After controlling for 15 confounding factors which included neighbourhood deprivation, education, number in household, smoking, markers of body size, inflammation, and glycated haemoglobin, these effect estimates were attenuated by 33% for Blacks, 52% for Asians and 43% for Other, but remained raised for Blacks (2.66; 1.82, 3.91), Asian (1.43; 0.91, 2.26) and other non-white groups (1.41; 0.87, 2.31). CONCLUSIONS AND RELEVANCE: Our findings show clear ethnic differences in risk of hospitalization for COVID-19 which do not appear to be fully explained by known explanatory factors. If replicated, our results have implications for health policy, including the targeting of prevention advice and vaccination coverage.


title: An eco-epidemiological study of Morbilli-related paramyxovirus infection in Madagascar bats reveals host-switching as the dominant macro-evolutionary mechanism

text: An eco-epidemiological investigation was carried out on Madagascar bat communities to better understand the evolutionary mechanisms and environmental factors that affect virus transmission among bat species in closely related members of the genus Morbillivirus, currently referred to as Unclassified Morbilli-related paramyxoviruses (UMRVs). A total of 947 bats were investigated originating from 52 capture sites (22 caves, 18 buildings, and 12 outdoor sites) distributed over different bioclimatic zones of the island. Using RT-PCR targeting the L-polymerase gene of the Paramyxoviridae family, we found that 10.5% of sampled bats were infected, representing six out of seven families and 15 out of 31 species analyzed. Univariate analysis indicates that both abiotic and biotic factors may promote viral infection. Using generalized linear modeling of UMRV infection overlaid on biotic and abiotic variables, we demonstrate that sympatric occurrence of bats is a major factor for virus transmission. Phylogenetic analyses revealed that all paramyxoviruses infecting Malagasy bats are UMRVs and showed little host specificity. Analyses using the maximum parsimony reconciliation tool CoRe-PA, indicate that host-switching, rather than co-speciation, is the dominant macro-evolutionary mechanism of UMRVs among Malagasy bats.


Introduction to the inaugural general issue of environment systems and decisions


title: Evaluation of the efficacy of disinfectants against Puumala hantavirus by real-time RT-PCR

text: Abstract Puumala virus, a hantavirus belonging to the Bunyaviridae family, causes a human disease known as nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome. The implementation of effective decontamination procedures is critical in hantavirus research to minimize the risk of personnel exposure. This study investigated the efficacy of Clidox®, Dettol®, ethanol, Halamid-d®, peracetic acid, sodium hypochloride and Virkon®S for inactivating Puumala virus. A real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to quantify Puumala virus before and after treatment with these products. Inactivation of Puumala virus was effective after 10min with all products except ethanol. Inactivation with absolute ethanol was effective only after 30min. Using the qRT-PCR method, this study has shown that the commercially available products Clidox®, Halamid-d® and Virkon®S in particular represent a rapid and safe way to decontaminate surfaces with possible Puumala virus contamination. These products can be used in solutions of 1–2%, with contact times greater than 10min, for inactivating effectively Puumala virus.


title: Perception of epidemic's related anxiety in the General French Population: a cross-sectional study in the Rhône-Alpes region

text: BACKGROUND: To efficiently plan appropriate public health interventions during possible epidemics, governments must take into consideration the following factors about the general population: their knowledge of epidemics, their fears of and psychological responses to them, their level of compliance with government measures and their communities' trusted sources of information. However, such surveys among the French general population are rare. METHODS: A cross-sectional study was conducted in 2006 in a representative sample of 600 subjects living in the Rhône-Alpes region (south-east France) to investigate self-reported knowledge about infectious diseases and anxiety generated by epidemic risk with particular reference to avian influenza. Data on reactions to potentially new epidemics and the confidence level in various sources of information were also collected. RESULTS: Respondents were most knowledgeable about AIDS, followed by avian influenza. Overall, 75% of respondents had adequate knowledge of avian influenza. The percentage was even higher (88%) among inhabitants of the Ain district, where an avian influenza epidemic had previously been reported. However, 39% expressed anxiety about this disease. In total, 20% of respondents with knowledge about avian influenza stated that they had changed their behaviours during the epizooty. Epidemics were perceived as a real threat by 27% of respondents. In the event of a highly contagious outbreak, the majority of respondents said they would follow the advice given by authorities. The study population expressed a high level of confidence in physicians and scientists, but had strong reservations about politicians, deputies and the media. CONCLUSIONS: Although the survey was conducted only four months after the avian influenza outbreak, epidemics were not perceived as a major threat by the study population. The results showed that in the event of a highly infectious disease, the population would comply with advice given by public authorities.


title: Can Teledentistry Improve the Monitoring of Patients during the Covid-19 Dissemination? A Descriptive Pilot Study

text: The aim of this pilot study was to describe the advantages of telemedicine (TM) in dental practice during the current national emergency condition due to the Covid-19 dissemination. At Department of Oral Surgery and Pathology—Magna Graecia University of Catanzaro, regional reference center for Covid-19—two groups of patients were determined: patients with urgent conditions (group U) and patients in follow-up (group F). Both groups were instructed to implement remote consultations using a messaging service (WhatsApp Messenger, WhatsApp Inc., Mountain View, California, USA) to send photos. A total of 418 photos were collected by 57 patients. Thirty-four photos were obtained by five patients in the U group after surgical procedures. All patients sent photos on the established evening, except for two patients who sent two photos outside the set days. In the F group, 384 photos were collected by 52 patients. None of them sent more photos than the number that was established by the protocol. Telemedicine allowed a monitoring of all patients, reducing costs and limiting human contact, decreasing the risk of Covid-19 dissemination.


title: Orthopaedic Surgical Selection and Inpatient Paradigms During the Coronavirus (COVID-19) Pandemic

text: The novel coronavirus pandemic, also known as SARS-CoV-2, has placed an immense strain on healthcare systems across the entire world. Consequently, multiple federal and state governments have placed restrictions on hospitals such as limiting “elective surgery” and recommending social or physical distancing. We review the literature on several areas that have been affected including surgical selection, inpatient care, and physician well-being. These areas affecting inpatient paradigms include surgical priority, physical or social distancing, file sharing for online clinical communications, and physician wellness. During this crisis, it is important that orthopaedic departments place an emphasis on personnel safety and slowing the spread of the virus so that the department can still maintain vital functions. Physical distancing and emerging technologies such as inpatient telemedicine and online file sharing applications can enable orthopaedic programs to still function while attempting to protect medical staff and patients from the novel coronavirus spread. This literature review sought to provide evidence-based guidance to orthopaedic departments during an unprecedented time. Orthopaedic surgeons should follow the Centers for Disease Control and Prevention guidelines, wear PPE when appropriate, have teams created using physical distancing, understand the department's policy on elective surgery, and engage in routines which enhance physician wellness.


title: Types of Renal Disease in Avian Species

text: Renal disease in birds is frequently encountered. Like most other animals, birds are susceptible to a full spectrum of renal insults,such as toxins, tumors, infections, and degenerative conditions. Accurate diagnosis of renal disease is based on a complete history,physical examination, and laboratory evaluation of the patient. Because it is often required for a more definitive diagnosis, special attention is given to histopathologic evaluation of renal tissue,whether through a premortem biopsy or collection at gross necropsy.


title: Community ‐and hospital laboratory‐based surveillance for respiratory viruses

text: Traditional surveillance for respiratory viruses relies on symptom detection and laboratory detection during medically attended encounters for acute respiratory infection/influenza‐like illness (ARI/ILI). Ecological momentary reporting using text messages is a novel method for surveillance. This study compares respiratory viral activity detected through longitudinal community‐based surveillance using text message responses for sample acquisition and testing to respiratory viral activity obtained from hospital laboratory data from the same community. We demonstrate a significant correlation between community‐ and hospital laboratory‐based surveillance for most respiratory viruses, although the relative proportions of viruses detected in the community and hospital differed significantly.


title: Parental Burnout and Child Maltreatment During the COVID-19 Pandemic

text: The novel coronavirus (COVID-19) has spread across the United States, resulting in significant changes in almost all aspects daily life. These changes place parents at increased risk for parental burnout. Parental burnout is a chronic condition resulting from high levels of parenting-related stress due to a mismatch between the demands of parenting and the resources available for parents to meet those demands. Research on parental burnout has suggested that parents who experience burnout are more likely to engage in child abuse and neglect, placing children at risk for detrimental short- and long-term outcomes. The purpose of this paper is to review the concept of parental burnout, discuss parental burnout in the context of the current COVID-19 pandemic, and focus specifically on the effects of child maltreatment. Implications for practitioners will be discussed.


title: Antiviral Activity Against Infectious Bronchitis Virus and Bioactive Components of Hypericum perforatum L.

text: Hypericum perforatum L., also known as Saint John’s Wort, has been well studied for its chemical composition and pharmacological activity. In this study, the antiviral activities of H. perforatum on infectious bronchitis virus (IBV) were evaluated in vitro and in vivo for the first time. The results of in vitro experiments confirmed that the antiviral component of H. perforatum was ethyl acetate extraction section (HPE), and results showed that treatment with HPE significantly reduced the relative messenger ribonucleic acid (mRNA) expression and virus titer of IBV, and reduced positive green immunofluorescence signal of IBV in chicken embryo kidney (CEK) cells. HPE treatment at doses of 480–120 mg/kg for 5 days, reduced IBV induced injury in the trachea and kidney, moreover, reduced the mRNA expression level of IBV in the trachea and kidney in vivo. The mRNA expression levels of IL-6, tumor necrosis factor alpha (TNF-α), and nuclear factor kappa beta (NF-κB) significantly decreased, but melanoma differentiation-associated protein 5 (MDA5), mitochondrial antiviral signaling gene, interferon alpha (IFN-α), and interferon beta (IFN-β) mRNA levels significantly increased in vitro and in vivo. Our findings demonstrated that HPE had significant anti-IBV effects in vitro and in vivo, respectively. In addition, it is possible owing to up-regulate mRNA expression of type I interferon through the MDA5 signaling pathway and down-regulate mRNA expression of IL-6 and TNF-α via the NF-κB signaling pathway. Moreover, the mainly active compositions of HPE analyzed by high-performance liquid chromatography/electrospray ionization–mass spectroscopy (ESI-MS) are hyperoside, quercitrin, quercetin, pseudohypericin, and hypericin, and a combination of these compounds could mediate the antiviral activities. This might accelerate our understanding of the antiviral effect of H. perforatum and provide new insights into the development of effective therapeutic strategies.


title: The receptor binding domain of MERS-CoV: The dawn of vaccine and treatment development

text: The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is becoming another “SARS-like” threat to the world. It has an extremely high death rate (∼50%) as there is no vaccine or efficient therapeutics. The identification of the structures of both the MERS-CoV receptor binding domain (RBD) and its complex with dipeptidyl peptidase 4 (DPP4), raises the hope of alleviating this currently severe situation. In this review, we examined the molecular basis of the RBD-receptor interaction to outline why/how could we use MERS-CoV RBD to develop vaccines and antiviral drugs.


title: Chapter 47 Issues and Challenges for Clinical Research in International Settings

text: Globalization, ease of travel, potential for spread of epidemics as well as widening health disparities between developed and resource-limited countries have made the need to conduct clinical research internationally a necessity. This reality calls for understanding the challenges and obstacles that can impact project outcome that must be overcome, to acquire new knowledge and disseminate evidence-based interventions to reduce global health disparities and inequities. These challenges include lack of an in-country skilled workforce, deficient infrastructure for research, inefficient health care system to support clinical research, poor data management, as well as inadequately structured institutional ethics boards and poor regulatory oversight. Investment in human capital development through training of research personnel, mentoring, increased support for research administration, engaging leaders in a community-engaged research partnership model prior to project initiation and wise use of technology for effective communication will promote robust clinical research in regions of the world where clinical research productivity historically has been exceedingly low.


title: Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic

text: BACKGROUND: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. METHODS: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I(2) statistics, and assessment of study quality. FINDINGS: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5–36·0] of 129 patients), depressed mood (42 [32·6%; 24·7–40·9] of 129), anxiety (46 [35·7%; 27·6–44·2] of 129), impaired memory (44 [34·1%; 26·2–42·5] of 129), and insomnia (54 [41·9%; 22·5–50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5–14·1] of 332 patients), insomnia (34 [12·1%; 8·6–16·3] of 280), anxiety (21 [12·3%; 7·7–17·7] of 171), irritability (28 [12·8%; 8·7–17·6] of 218), memory impairment (44 [18·9%; 14·1–24·2] of 233), fatigue (61 [19·3%; 15·1–23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9–37·3] of 181) and sleep disorder (14 [100·0%; 88·0–100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7–42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1–18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1–19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1–84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. INTERPRETATION: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. FUNDING: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.


title: Thoughts on Intervention in HIV/AIDS with Traditional Chinese Medicine

text: Abstracts HIV/AIDS has become a worldwide pandemic and highly active antiretroviral therapy (HAART) is the only generally recognized effective therapy at present. However, various unresolvable problems appear with the widespread use of HAART. Traditional Chinese Medicine shows good efficacy for intervention in HIV/AIDS and could become an effective treatment option.


title: Multiple molecular detection of respiratory viruses and associated signs of airway inflammation in racehorses

text: BACKGROUND: The potential involvement of viruses in inflammatory airway disease (IAD) was previously investigated through either serology or PCR from nasopharyngeal swabs (NS). The aims of this study were to determine the prevalence and incidence of viral genome detection by qPCR in the equine airways, and their association with respiratory clinical signs. METHODS: Both NS and tracheal washes (TW) were collected monthly on 52 Standardbred racehorses at training, over 27 consecutive months (581 samples). Equid herpesviruses (EHV)-1, −4, −2 and −5, equine rhinitis virus-A and -B (ERBV), equine adenovirus-1 and −2, equine coronavirus and equine influenza virus were systematically investigated in both NS and TW. Nasal discharge, coughing, tracheal mucus score and TW neutrophil proportions were simultaneously recorded. RESULTS: Genome for 7/10 viruses were detected at least once throughout the study; up to 4 different viruses being also concomitantly detected. Monthly incidence in TW was respectively 27.9% (EHV-5), 24.8% (EHV-2), 7.1% (ERBV), 3.8% (EHV-4), 1.9% (EAdV1) and 0.2% (EHV-1; ERAV). Neither agreement nor correlation between NS and TW was found for respectively genome detection and viral loads. Detection of viral genome in NS was not associated with any clinical sign. Coughing was significantly associated with TW detection of EHV-2 DNA (OR 3.1; P = 0.01) and ERBV RNA (OR 5.3; P < 0.001). Detection of EHV-2 DNA in TW was also significantly associated with excess tracheal mucus (OR 2.1; P = 0.02). CONCLUSIONS: Detection and quantification of EHV-2 and ERBV by qPCR in TW, but not in NS, should be considered when investigating horses with IAD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0657-5) contains supplementary material, which is available to authorized users.


title: Diagnostic moléculaire en pathologie infectieuse: intérêt d'un diagnostic multiplex dans les pneumopathies atypiques

text: Résumé Parmi les pathogènes responsables de pneumopathies atypiques, Mycoplasma pneumoniae, Chlamydia pneumoniae, et Legionella pneumophila sont trois bactéries fréquentes pour lesquelles un diagnostic étiologique rapide est difficile à obtenir. L'amplification génique in vitro offre une possibilité de rendu de résultats dans la journée, mais souvent au détriment d'un temps de réalisation important du fait du manque d'automatisation. Cet inconvénient est réduit en cas d'utilisation de techniques d'amplification génique multiplex, dont un exemple de réalisation est présenté dans cet article. Abstract Among frequent potential respiratory pathogens, Mycoplasma pneumoniæ, Chlamydia pneumoniæ, and Legionella pneumophila are difficult to isolate with usual laboratory techniques (culture, serologic tests). Adapted molecular biology tools are able to amplify a specific genomic target and allow the diagnosis the same day, but with a very time consuming process. The proposed technique allows the diagnosis of the three bacteriaes in a few hours time using a multiplex single-tube polymerase chain reaction.


title: Urticaire de l’enfant

text: Résumé L’incidence cumulée de l’urticaire chez l’enfant est proche de 10 %. On décrit la forme superficielle et la forme profonde, ou angioedème. Chez le jeune enfant de moins de 3 ans, l’urticaire est volontiers annulaire et ecchymotique et prise à tort pour un érythème polymorphe ou un œdème aigu hémorragique. La pseudo-maladie sérique est une forme particulière d’urticaire caractérisée par un angioedème des extrémités, une fièvre et des arthralgies, la principale cause est médicamenteuse (céphalosporines). Chez l’enfant, l’interrogatoire et l’examen clinique sont essentiels et permettent dans la plupart des cas de mettre en évidence une étiologie. Les principales causes d’urticaire aiguë ou récidivante sont les infections virales et/ou les médicaments (histaminolibération non spécifique), alors que les urticaires chroniques sont majoritairement de cause physique. Dans les pays développés, les infections parasitaires sont rarement en cause. Les arguments en faveur d’une allergie alimentaire sont : un contexte d’atopie, la survenue dans l’heure suivant la prise de l’aliment suspect, l’absence de fièvre ou de contexte infectieux, la durée inférieure à 24heures, l’association éventuelle à d’autres manifestations d’anaphylaxie et la récidive à chaque nouvelle prise de l’aliment suspect. Le traitement de première intention d’une urticaire sans signe de gravité se limite à la prescription d’un antihistaminique non sédatif (associé à l’éviction de la cause lorsque celle-ci est déterminée). Près d’un tiers des cas d’urticaire de l’enfant évolue sur une durée prolongée de plus de 6 semaines, définissant l’urticaire chronique (le plus souvent à type d’urticaire récidivante bénigne lors des épisodes infectieux et/ou la prise de médicaments). Il est très rare qu’une urticaire, même chronique, révèle une maladie inflammatoire ou une maladie génétique comme une cryopyrinopathie, le bilan étiologique de première intention se limite habituellement aux examens suivants : NFS, VS et/ou CRP, transaminases. Abstract The cumulative incidence of urticaria in children is close to 10%. Two forms are described: the superficial form and the deep form, or angioedema. In young children aged under 3 years, urticaria is commonly annular and ecchymotic, and is mistaken for erythema multiforme or acute hemorrhagic edema. Serum sickness-like reaction is a particular form of urticaria characterized by angioedema of the extremities, fever and arthralgia, and it is chiefly drug-induced (cephalosporins). With children, questioning and clinical examination are essential and, in most cases, reveal an etiology. The main causes of acute or recurrent urticaria are viral infections and/or drugs (non-specific histamine release), whereas chronic urticaria is mostly due to physical causes. In developed countries, parasitic infections are rarely the cause. Arguments in favor of a food allergy are as follows: a setting of atopy, onset within one hour of taking the suspect food, absence of fever or infection, a duration of less than 24hours, possible association with other signs of anaphylaxis, and further recurrence with each new intake of the suspect food. First-line treatment of urticaria without signs of severity consists solely of non-sedating antihistamine (associated with removal of the cause where the latter has been determined). Nearly one-third of cases of urticaria in children progress over a prolonged period of more than 6 weeks, thus constituting chronic urticaria (most often a form of mild recurrent urticaria during episodes of infection and/or medication). Chronic urticaria is very rarely due to an underlying inflammatory disease or a genetic disease such as cryopyrinopathy, and first-line etiological assessment is usually limited to the following tests: CBC, sedimentation speed and/or CRP, and transaminases.


title: Characterization of a Novel Bat Adenovirus Isolated from Straw-Colored Fruit Bat (Eidolon helvum)

text: Bats are important reservoirs for emerging zoonotic viruses. For extensive surveys of potential pathogens in straw-colored fruit bats (Eidolon helvum) in Zambia, a total of 107 spleen samples of E. helvum in 2006 were inoculated onto Vero E6 cells. The cell culture inoculated with one of the samples (ZFB06-106) exhibited remarkable cytopathic changes. Based on the ultrastructural property in negative staining and cross-reactivity in immunofluorescence assays, the virus was suspected to be an adenovirus, and tentatively named E. helvum adenovirus 06-106 (EhAdV 06-106). Analysis of the full-length genome of 30,134 bp, determined by next-generation sequencing, showed the presence of 28 open reading frames. Phylogenetic analyses confirmed that EhAdV 06-106 represented a novel bat adenovirus species in the genus Mastadenovirus. The virus shared similar characteristics of low G + C contents with recently isolated members of species Bat mastadenoviruses E, F and G, from which EhAdV 06-106 diverged by more than 15% based on the distance matrix analysis of DNA polymerase amino acid sequences. According to the taxonomic criteria, we propose the tentative new species name “Bat mastadenovirus H”. Because EhAdV 06-106 exhibited a wide in vitro cell tropism, the virus might have a potential risk as an emerging virus through cross-species transmission.


Safety of cancer surgery during the COVID‐19 pandemic


title: If You’re Ready, I Am Ready (But the Wait Is Harming Us Both) Individual Risks in Institutional Conversions

text: Rambo, Adele, and a religion professor walk into a coffee shop. What in the world do they have in common? This essay integrates Lewis Rambo’s scholarship on conversion with pop singer Adele’s popular song “Send My Love to Your Lover” to understand and redress inequity in individual risk within processes of institutional conversion. The author focuses on practices of inclusion in institutions of higher education using the specific example of theological schools with aspirational school mission statements that embrace equity and diversities. She argues that bringing Rambo and Adele into conversation with anecdotal and published research on institutional (in)justice illuminates four practices that institutions could adopt to better align practice with promise and thereby promote wellness for all who are impacted by institutional health.


title: Modified vaccinia virus Ankara as antigen delivery system: how can we best use its potential?

text: Safety-tested modified vaccinia virus Ankara (MVA) has been established as a potent vector system for the development of candidate recombinant vaccines. The versatility of the vector system was recently demonstrated by the rapid production of experimental MVA vaccines for immunization against severe acute respiratory syndrome associated coronavirus. Promising results were also obtained in the delivery of Epstein-Barr virus or human cytomegalovirus antigens and from the clinical testing of MVA vectors for vaccination against immunodeficiency virus, papilloma virus, Plasmodium falciparum or melanoma. Moreover, MVA is considered to be a prime candidate vaccine for safer protection against orthopoxvirus infections. Thus, vector development to challenge dilemmas in vaccinology or immunization against poxvirus biothreat seems possible, yet the right choice should be made for a most beneficial use.


title: Middle east respiratory syndrome corona virus (MERS CoV): The next steps

text: Developing countries are at risk of importing Middle East Respiratory Syndrome Corona Virus (MERS CoV) from the Middle East. Hospitals in the Middle East currently reporting the disease are staffed by immigrants. In the current hot spots for MERS CoV a sizeable portion of the population is from other countries, but many of these countries have yet to detect any importation of MERS CoV. To assess the disease transmission in these countries, supplemental surveillance strategies are urgently needed beyond the currently recommended measures. A few strategies to address the situation are: (i) improving preparedness with enhanced surveillance in particular regions; (ii) targeting certain sentinel groups for surveillance in hot spots; and (iii) limited use of serosurveillance. Recovered, immune patients can be employed to give patient care during outbreaks.


title: A recombinant VSV-vectored MERS-CoV vaccine induces neutralizing antibody and T cell responses in rhesus monkeys after single dose immunization

text: Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) has been a highly threatening zoonotic pathogen since its outbreak in 2012. Similar to SARS-CoV, MERS-CoV belongs to the coronavirus family and can induce severe respiratory symptoms in humans, with an average case fatality rate of 35% according to the World Health Organization. Spike (S) protein of MERS-CoV is immunogenic and can induce neutralizing antibodies, thus is a potential major target for vaccine development. Here we constructed a chimeric virus based on the vesicular stomatitis virus (VSV) in which the G gene was replaced by MERS-CoV S gene (VSVΔG-MERS). The S protein efficiently incorporated into the viral envelope and mediated cell entry through binding its receptor, human DPP4. Knockdown of clathrin expression by siRNA drastically abrogated the infection of VSVΔG-MERS in Vero cells. Furthermore, in animal studies, the recombinant virus induced neutralizing antibodies and T cell responses in rhesus monkeys after a single intramuscular or intranasal immunization dose. Our findings indicate the potential of the chimeric VSVΔG-MERS as a rapid response vaccine candidate against emerging MERS-CoV disease.


title: Canine coronavirus, Greece. Molecular analysis and genetic diversity characterization

text: Abstract Canine coronavirus (CCoV) is an etiologic agent of diarrhea in dogs and is known to have spread worldwide. Mild disease or asymptomatic carriage are probably in many cases common outcomes of infection. To date, two different genotypes of CCoV are known, CCoV type I (CCoV-I) and CCoV type II (CCoV-II). CCoV type II is divided in two subtypes, CCoV-IIa (classical strains) and CCoV-IIb, with CCoV-IIb emerging as a result of a putative recombination between CCoV-IIa and transmissible gastroenteritis virus (TGEV). The aim of the present study was to investigate the presence of CCoV in Greece and to genetically analyze the circulating strains. Between December 2007 and December 2009, 206 fecal samples were collected from dogs with diarrhea from kennels, pet shops and veterinary clinics of different country regions. RT-PCR and real time RT-PCR assays were used for CCoV detection and characterization. CCoV was identified in 65.1% of the dogs presenting diarrhea, being more frequently detected in animals younger than 3months old and in animals housed in groups. In 47% of the positive samples more than one CCoV genotype/subtype were detected, with triple CCoV-I/CCoV-IIa/CCoV-IIb infections being identified for the first time. Molecular and phylogenetic analysis revealed that CCoV-I Greek strains share low genetic relatedness to each other and to the prototype CCoV-I strains in the 5’ end of the S gene. Moreover, a divergent CCoV-IIa strain was identified. The circulation of highly variable CCoV-I and CCoV-IIb emerging strains, as well as the detection of the divergent strain, raise concerns on the importance of these new strains as primary pathogens of diarrhoeic syndromes diagnosed in dogs.


title: Isatis indigotica root polysaccharides as adjuvants for an inactivated rabies virus vaccine

text: Abstract Adjuvants can enhance vaccine immunogenicity and induce long-term enhancement of immune responses. Thus, adjuvants are important for vaccine research. Polysaccharides isolated from select Chinese herbs have been demonstrated to possess various beneficial functions and excellent adjuvant abilities. In the present study, the polysaccharides IIP-A-1 and IIP-2 were isolated from Isatis indigotica root and compared with the common vaccine adjuvant aluminum hydroxide via intramuscular co-administration of inactivated rabies virus rCVS-11-G into mice. Blood was collected to determine virus neutralizing antibody (VNA) titers and B and T lymphocyte activation status. Inguinal lymph node samples were collected and used to measure B lymphocyte proliferation. Splenocytes were isolated, from which antigen-specific cellular immune responses were detected via ELISpot, ELISA and intracellular cytokine staining. The results revealed that both types of polysaccharides induce more rapid changes and higher VNA titers than aluminum hydroxide. Flow cytometry assays revealed that the polysaccharides activated more B lymphocytes in the lymph nodes and more B and T lymphocytes in the blood than aluminum hydroxide. Antigen-specific cellular immune responses showed that IIP-2 strongly induced T lymphocyte proliferation in the spleen and high levels of cytokine secretion from splenocytes, whereas aluminum hydroxide induced proliferation in only a small number of lymphocytes and the secretion of only small quantities of cytokines. Collectively, these data suggest that the polysaccharide IIP-2 exhibits excellent adjuvant activity and can enhance both cellular and humoral immunity.


title: Relationship Between Odor Intensity Estimates and COVID-19 Prevalence Prediction in a Swedish Population

text: In response to the coronavirus disease 2019 (COVID-19) pandemic, countries have implemented various strategies to reduce and slow the spread of the disease in the general population. For countries that have implemented restrictions on its population in a stepwise manner, monitoring of COVID-19 prevalence is of importance to guide the decision on when to impose new, or when to abolish old, restrictions. We are here determining whether measures of odor intensity in a large sample can serve as one such measure. Online measures of how intense common household odors are perceived and symptoms of COVID-19 were collected from 2440 Swedes. Average odor intensity ratings were then compared to predicted COVID-19 population prevalence over time in the Swedish population and were found to closely track each other (r = −0.83). Moreover, we found that there was a large difference in rated intensity between individuals with and without COVID-19 symptoms and the number of symptoms was related to odor intensity ratings. Finally, we found that individuals progressing from reporting no symptoms to subsequently reporting COVID-19 symptoms demonstrated a large drop in olfactory performance. These data suggest that measures of odor intensity, if obtained in a large and representative sample, can be used as an indicator of COVID-19 disease in the general population. Importantly, this simple measure could easily be implemented in countries without widespread access to COVID-19 testing or implemented as a fast early response before widespread testing can be facilitated.


title: Non‐proteolytic functions of microbial proteases increase pathological complexity

text: Proteases are enzymes that catalyse hydrolysis of peptide bonds thereby controlling the shape, size, function, composition, turnover and degradation of other proteins. In microbes, proteases are often identified as important virulence factors and as such have been targets for novel drug design. It is emerging that some proteases possess additional non‐proteolytic functions that play important roles in host epithelia adhesion, tissue invasion and in modulating immune responses. These additional “moonlighting” functions have the potential to obfuscate data interpretation and have implications for therapeutic design. Moonlighting enzymes comprise a subcategory of multifunctional proteins that possess at least two distinct biological functions on a single polypeptide chain. Presently, identifying moonlighting proteins relies heavily on serendipitous empirical data with clues arising from proteins lacking signal peptides that are localised to the cell surface. Here, we describe examples of microbial proteases with additional non‐proteolytic functions, including streptococcal pyrogenic exotoxin B, PepO and C5a peptidases, mycoplasmal aminopeptidases, mycobacterial chaperones and viral papain‐like proteases. We explore how these non‐proteolytic functions contribute to host cell adhesion, modulate the coagulation pathway, assist in non‐covalent folding of proteins, participate in cell signalling, and increase substrate repertoire. We conclude by describing how proteomics has aided in moonlighting protein discovery, focusing attention on potential moonlighters in microbial exoproteomes.


Dynamic and integrative approaches to understanding pathogen spillover


title: Meta-analysis investigating the relationship between clinical features, outcomes, and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia

text: OBJECTIVE: We aimed to investigate the relationship between clinical characteristics, outcomes and the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. METHODS: We performed a systematic review and meta-analysis using PubMed, Embase, and Cochrane Library databases to assess the clinical characteristics and outcomes of confirmed COVID-19 cases and compared severe (ICU) and non-severe (non-ICU) groups. RESULTS: We included 12 cohort studies including 2445 patients with COVID-19. Compared with non-severe (non-ICU) patients, severe (ICU) disease was associated with a smoking history (P=0.003) and comorbidities including chronic obstructive pulmonary disease (OR=5.08, P<0.001), diabetes (OR=3.17, P<0.001), hypertension (OR=2.40, P<0.001), coronary heart disease (OR=2.66, P<0.001), cerebrovascular diseases (OR=2.68, P=0.008), and malignancy (OR=2.21, P=0.040). We found significant differences between the two groups for fever, dyspnea, decreased lymphocyte and platelet counts, and increased leukocyte count, C-creative protein, procalcitonin, lactose dehydrogenase, aspartate aminotransferase, alanine aminotransferase, creatinine kinase, and creatinine levels (P<0.05). Significant differences were also observed for multiple treatments (P<0.05). Patients in the severe (ICU) group were more likely to have complications and had a much higher mortality rate and lower discharge rate than those with non-severe (non-ICU) disease (P<0.05). CONCLUSIONS: Investigation of clinical characteristics and outcomes of severe cases of COVID-19 will contribute to early prediction, accurate diagnosis, and treatment to improve the prognosis of patients with severe illness.


title: Approaching COVID‐19 ‐ bedside strategies for intensive care

text: The spread of novel coronavirus disease (COVID‐19) urged a never‐seen coordinated global response to prepare the health system, including primary care, hospital facilities and intensive care units (ICUs). Lessons have been learned from countries who suffered the pandemic at the beginning, helping the ones which are on different phases of the spreading curve. Currently, optimizing intensive care resources is mandatory as admittance to the ICUs remains rising exponentially. While public and private health system struggle for changing the slope of the curve, intensivists prepare the facilities for a tsunami of respiratory failure patients with COVID‐19.(1)


title: Characterization of a genetically heterogeneous porcine rotavirus C, and other viruses present in the fecal virome of a non-diarrheic Belgian piglet

text: Abstract Next-generation sequencing (NGS) technologies are becoming increasingly accessible, leading to an expanded interest in the composition of the porcine enteric virome. In the present study, the fecal virome of a non-diarrheic Belgian piglet was determined. Although the virome of only a single piglet was analyzed, some interesting data were obtained, including the second complete genome of a pig group C rotavirus (RVC). This Belgian strain was only distantly related to the only other completely characterized pig RVC strain, Cowden. Its relatedness to RVC strains from other host species was also analyzed and the porcine strain found in our study was only distantly related to RVCs detected in humans and cows. The gene encoding the outer capsid protein VP7 belonged to the rare porcine G3 genotype, which might be serologically distinct from most other pig RVC strains. A putative novel RVC VP6 genotype was identified as well. A group A rotavirus strain also present in this fecal sample contained the rare pig genotype combination G11P[27], but was only partially characterized. Typical pig RVA genotypes I5, A8, and T7 were found for the viral proteins VP6, NSP1, and NSP3, respectively. Interestingly, the fecal virome of the piglet also contained an astrovirus and an enterovirus, of which the complete genomes were characterized. Results of the current study indicate that many viruses may be present simultaneously in fecal samples of non-diarrheic piglets. In this study, these viruses could not be directly associated with any disease, but still they might have had a potential subclinical impact on pig growth performance. The fast evolution of NGS will be a powerful tool for future diagnostics in veterinary practice. Its application will certainly lead to better insights into the relevance of many (sub)clinical enteric viral infections, that may have remained unnoticed using traditional diagnostic techniques. This will stimulate the development of new and durable prophylactic measures to improve pig health and production.


title: Triggering unfolded protein response by 2-Deoxy-d-glucose inhibits porcine epidemic diarrhea virus propagation

text: Abstract The unfolded protein response (UPR) is cyto-protective machinery elicited towards an influx of large amount of protein synthesis in the endoplasmic reticulum (ER). Extensive studies suggest that the UPR can also be activated during virus infection. In the present studies, we first evaluated if porcine epidemic diarrhea virus (PEDV) infection activated the UPR pathways. Electron microscopy analysis demonstrated the morphology changes of ER post-PEDV infection. Western blot and real-time PCR identified the differences of UPR genes in response to PEDV infection. The results suggested that PEDV infection induced UPR in Vero cells. Meanwhile, we silenced the expression of PKR-like ER kinase (PERK) by shRNA, we found that the knockdown of PERK increased virus loads in the cells, which was consistent with the result on 4-phenylbutyrate (4-PBA) treatment. We next determined whether 2-Deoxy-d-glucose (2-DG), an ER stress inducer, possessed antiviral activity against PEDV infection. Plaque formation assay, RT-PCR and Western blot analysis suggested that 2-DG might inhibit virus infection by affecting viral protein translation during the early stage of virus infection. Interestingly, we also found that 2-DG treatment could affect virus assembly, which is similar to previous studies on influenza virus. All these results support the therapeutic potential of using 2-DG or glucose/mannose analogs to induce the UPR to block virus replication.


title: COVID-19 Presenting with Seizures

text: Abstract This case report examines a male with no previous history of seizures initially admitting to the medical service later upgraded to ICU after respiratory failure developing multiple episodes of seizures. Laboratory values on admission, neurological investigations, as well as review of current literature on COVID-19 encephalitis is provided.


title: Radiology department strategies to protect radiologic technologists against COVID19: Experience from Wuhan

text: Abstract The outbreak of Coronavirus Disease 2019 (COVID-19) is a huge threat to global public health security. In the absence of specific antiviral medicines to prevent or treat COVID-19, it is essential to detect the infected patients at an early stage and immediately isolate them from the healthy population. In view of the advantages of sensitivity and high spatial resolution, CT imaging has played an important role in screening and diagnosing of COVID-19 in China. The radiologic technologists performing CT scans for the infected patients become high-risk medical care personnel. It is critical for the radiology department to ensure the personal safety of radiologic technologists and avoid cross-infection. In this review article, we describe the systematic strategies to combat COVID-19 from the radiology department in Tongji hospital in Wuhan, P.R. China, including personnel arrangements, environmental modification, protection levels and configurations, radiological imaging (CT and radiography), and disinfection methods. It can provide guidance to other radiology departments faced with COVID-19 to reduce infection risk for radiologic technologists.


title: Coronavirus: la emergencia geriátrica de 2020. Documento conjunto de la Sección de Cardiología Geriátrica de la Sociedad Española de Cardiología y la Sociedad Española de Geriatría y Gerontología

text: Resumen La infección por SARS-CoV-2, denominada COVID-19 (Coronavirus Infectious Disease-19), es una enfermedad desconocida hasta diciembre de 2019 a la que nos enfrentamos en España desde el 31 de enero de 2020 —fecha del primer caso diagnosticado en nuestro país— y que ya ha causado la muerte de 7.340 personas (a 30 de marzo de 2020), sobre todo mayores. Es importante tener en cuenta que, dado que la información evoluciona con extremada rapidez en este campo, lo expuesto en el presente documento puede estar sujeto a modificaciones. La población de mayor edad es especialmente susceptible a la infección por COVID-19, así como a desarrollar criterios de gravedad. Este aumento de morbimortalidad en el paciente mayor se ha asociado tanto con las comorbilidades, especialmente la enfermedad cardiovascular, como con la situación de fragilidad, que conlleva una respuesta inmunológica más pobre. La situación actual, tanto por los países afectados como por el número de casos, constituye una pandemia y supone una emergencia sanitaria de primer nivel. Como España es uno de los países más envejecidos del mundo, la COVID-19 se ha convertido en una emergencia geriátrica. El presente documento se ha elaborado conjuntamente entre la Sección de Cardiología Geriátrica de la Sociedad Española de Cardiología y la Sociedad Española de Geriatría y Gerontología. Abstract SARS-CoV2 infection, also known as COVID-19 (coronavirus infectious disease-19), was first identified in December 2019. In Spain, the first case of this infection was diagnosed on 31 January, 2020 and, by 30 March 2020, has caused 7340 deaths, especially in the elderly. Due to the rapidly evolving situation regarding this disease, the data reported in this article may be subject to modifications. The older population are particularly susceptible to COVID-19 infection and to developing severe disease. The higher morbidity and mortality rates in older people have been associated with comorbidity, especially cardiovascular disease, and frailty, which weakens the immune response. Due to both the number of affected countries and the number of cases, the current situation constitutes an ongoing pandemic and a major health emergency. Because Spain has one of the largest older populations in the world, COVID-19 has emerged as a geriatric emergency. This document has been prepared jointly between the Geriatric Cardiology Section of the Spanish Society of Cardiology and the Spanish Society of Geriatrics and Gerontology.


title: CHAPTER 9 Low-molecular-weight S-nitrosothiols

text: Publisher Summary This chapter is primarily concerned with the S-nitrosothiols of low molecular weight. S-nitrosothiols (thionitrites, RSNO) appear as endogenous reaction products of NO or NO metabolites with sulfhydryl groups. Prime targets are the sulfhydryl groups on cysteine residues found in many different proteins or the thiol moieties on endogenous glutathione (GSH) or cysteine (Cys). The nitrosation of the sulfhydryl moiety leads to S-nitrosothiols with high and low molecular weight, respectively. The interest in the S-nitrosothiols was motivated by the observation that these compounds form in vivo and may elicit physiological responses that are strongly reminiscent of free NO radicals. Well-documented examples are vasodilation and the inhibition of platelet aggregation.