title: The discovery of angiotensin‐converting enzyme 2 and its role in acute lung injury in mice

text: During several months of 2002, severe acute respiratory syndrome (SARS) caused by SARS‐coronavirus (SARS‐CoV) spread rapidly from China throughout the world, causing more than 800 deaths due to the development of acute respiratory distress syndrome (ARDS), which is the severe form of acute lung injury (ALI). Interestingly, a novel homologue of angiotensin‐converting enzyme, termed angiotensin‐converting enzyme 2 (ACE2), has been identified as a receptor for SARS‐CoV. Angiotensin‐converting enzyme and ACE2 share homology in their catalytic domain and provide different key functions in the renin–angiotensin system (RAS). Angiotensin‐converting enzyme cleaves angiotensin I to generate angiotensin II, which is a key effector peptide of the system and exerts multiple biological functions, whereas ACE2 reduces angiotensin II levels. Importantly, our recent studies using ACE2 knockout mice have demonstrated that ACE2 protects murine lungs from ARDS. Furthermore, SARS‐CoV infections and the Spike protein of the SARS‐CoV reduce ACE2 expression. Notably, injection of SARS‐CoV Spike into mice worsens acute lung failure in vivo, which can be attenuated by blocking the renin–angiotensin pathway, suggesting that the activation of the pulmonary RAS influences the pathogenesis of ALI/ARDS and SARS.


title: Marqueurs biologiques de gravité initiale des bronchiolites aiguës et d’évolution vers un asthme du nourrisson

text: Acute bronchiolitis is an acute respiratory infection which commonly occurs in infancy. Respiratory syncytial virus is the major cause of lower respiratory tract infection. Some other virus may be found during co-infections. The aim of this study was to search for biological markers correlated with gravity and risk factors for asthma and allergy. The follow up was done during the multicenter and prospective study Bronchiolitis (PHRC 2000 n° 2000/020/HP), performed between November 2001 and January 2006, which included seven centers in France: Rouen, Le Havre, Lille, Elbeuf, Evreux, Brest and Saint-Nazaire associated with Nantes. Clinical an biological data were gathered during initial course, then at one month and one year. For the population of 209 infants mean aged was 3 month, the gravity was evaluated by scoring. The laboratory results correlated with clinical scoring were the following: viral evaluation, absolute numbers of leucocytes, lymphocytes and eosinophils, flow cytometry for sub-populations of lymphocytes, allergology including IgE, eosinophilic cationic protein, and basophil activation test. The results of the study are presented and discussed.


title: Strengthening the Power of Nurses in Combating COVID‐19

text: In December 2019, several novel coronavirus infections were firstly reported in Wuhan, Hubei Province in China, and the outbreak is quickly expanding locally and globally. World Health Organization (World Health Organization, 2020a) announced the coronavirus epidemic as an “International Public Health Emergency of International Concern (PHEIC)” on January 30, 2020.


title: Association of Radiologic Findings with Mortality in Patients with Avian Influenza H7N9 Pneumonia

text: BACKGROUND: The novel H7N9 virus causes severe illness, including pneumonia and acute respiratory distress syndrome, with high rates of mortality. We investigated the association of initial radiologic characteristics obtained at admission with clinical outcomes in patients with avian influenza H7N9 pneumonia. METHODS: Demographics, comorbidities, clinical findings, radiologic appearance and scores of the affected lung parenchyma were compared between survivor group (n = 15) and mortality group (n = 7). Two radiologic scores were calculated, one using chest radiography and one using CT. Follow-up CT scans at discharge were analyzed in 12 patients of the survival group. RESULTS: All the patients in mortality group developed acute respiratory distress syndrome and required mechanical ventilation, while in the survival group 33% (5/15) developed acute respiratory distress syndrome (P<0.05) and 27% (4/15) required mechanical ventilation (P<0.05). The mean radiographic and CT scores of the mortality group were 50% higher compared to the survival group (P<0.05). ROC analysis revealed an area under curve of 0.738 for the radiographic score with an optimal cutoff value of a score of 19 for prediction of mortality, with a sensitivity of 71% and a specificity of 67%, and an area under curve of 0.833 for the CT score with an optimal cutoff value of a CT score of 21 for prediction of mortality, with a sensitivity of 86% and a specificity of 73%. The mean CT score of the affected lung parenchyma at discharge was 30% lower than the initial CT examination (P<0.05). CONCLUSION: High initial radiologic score is associated with mortality in patients with avian influenza H7N9 pneumonia.


title: High-throughput assay using a GFP-expressing replicon for SARS-CoV drug discovery

text: Abstract The causative agent of severe acute respiratory syndrome (SARS) has been identified as a novel coronavirus, SARS-CoV. The development of rapid screening assays is essential for antiviral drug discovery. By using a cell line expressing a SARS-CoV subgenomic replicon, we developed a high-throughput assay and used it to screen small molecule compounds for inhibitors of SARS-CoV replication in the absence of live virus. The assay system involves minimal manipulation after assay set-up, facilitates automated read-out and minimizes risks associated with hazardous viruses. Based on this assay system, we screened 7035 small molecule compounds from which we identified 7 compounds with anti-SARS-CoV activity. We demonstrate that the compounds inhibited SARS-CoV replication-dependent GFP expression in the replicon cells and reduced SARS-CoV viral protein accumulation and viral RNA copy number in the replicon cells. In a SARS-CoV plaque reduction assay, these compounds were confirmed to have antiviral activity. The target of one of the hit compounds, C12344, was validated by the generation of resistant replicon cells and the identification of the mutations conferring the resistant phenotype. These compounds should be valuable for developing anti-SARS therapeutic drugs as well as research tools to study the mechanism of SARS-CoV replication.


title: Antimicrobial susceptibility and phylotyping profile of pathogenic Escherichia coli and Salmonella enterica isolates from calves and pigs in Minas Gerais, Brazil

text: The aims of the present study were to determine (i) the profiles of phylogroup and (ii) the antimicrobial susceptibility of pathogenic Escherichia coli strains isolated from calves, and of Salmonella spp. strains isolated from calves and pigs in Minas Gerais State, Brazil. Sixty-one pathogenic E. coli strains and Salmonella spp. (n = 24) strains isolated from fecal samples of calves and Salmonella spp. (n = 39) strains previously isolated from fecal samples of growing/finishing pigs were tested. The minimum inhibitory concentration (MIC) using the agar dilution method was determined for nalidixic acid, amikacin, amoxicillin, ampicillin, cefoxitin, norfloxacin, gentamicin, tetracycline, and trimethoprim-sulfamethoxazole. All E. coli isolates were susceptible to amikacin. Tetracycline was the antimicrobial that presented the higher frequency of resistance among E. coli strains, followed by ampicillin, trimethoprim-sulfamethoxazole, amoxicillin, nalidixic acid, norfloxacin, gentamicin, and cefoxitin. E. coli (n = 61) strains isolated from calves belonged to different phylogroup namely, phylogroup A (n = 26), phylogroup B1 (n = 31), phylogroup E (n = 3), and phylogroup F (n = 1). Phylogroups B2, C, and D were not identified among the E. coli in the present study. All Salmonella spp. (n = 24) strains isolated from fecal samples of calves were susceptible to amikacin, amoxicillin, ampicillin, norfloxacin, gentamicin, tetracycline, and trimethoprim-sulfamethoxazole. Resistance to nalidixic acid and cefoxitin was detected in 16.66 and 8.33 % of the Salmonella spp. strains, respectively. Among the Salmonella spp. (n = 39) strains isolated from fecal samples of pigs, the higher frequency of resistance was observed to tetracycline, followed by amoxicillin, gentamicin, ampicillin, trimethoprim-sulfamethoxazole, nalidixic acid, cefoxitin, and norfloxacin. All strains were susceptible to amikacin. Forty-eight (78.68 %) of the E. coli strains were classified as multidrug-resistant, whereas among Salmonella spp. strains, the percentage of multidrug resistance was 57.14 %, being all multidrug-resistant strains isolated from pigs (92.30 %). The results from the present study indicate a high frequency of antimicrobial resistance among pathogenic E. coli strains isolated from calves and Salmonella spp. strains isolated from pigs and a high rate of susceptibility to most antimicrobials tested among Salmonella spp. strains isolated from calves. Our study highlights the presence of multidrug-resistant strains of E. coli and Salmonella spp. isolated from food-producing animals in Minas Gerais, Brazil. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11250-016-1152-0) contains supplementary material, which is available to authorized users.


Using Telehealth as a Tool for Rural Hospitals in the COVID‐19 Pandemic Response


title: Computational methods for drug design and discovery: focus on China

text: In the past decades, China's computational drug design and discovery research has experienced fast development through various novel methodologies. Application of these methods spans a wide range, from drug target identification to hit discovery and lead optimization. In this review, we firstly provide an overview of China's status in this field and briefly analyze the possible reasons for this rapid advancement. The methodology development is then outlined. For each selected method, a short background precedes an assessment of the method with respect to the needs of drug discovery, and, in particular, work from China is highlighted. Furthermore, several successful applications of these methods are illustrated. Finally, we conclude with a discussion of current major challenges and future directions of the field.


title: Sepsis due to Streptococcus pneumoniae associated with secondary hemophagocytic lymphohistiocytosis in a splenectomized patient for spherocytosis: A case report

text: RATIONALE: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome that is characterized by an inappropriate hyperinflammatory immune response – primary, as a consequence of a genetic defect of NK cells and cytotoxic T lymphocytes or – secondary, in the progression of infections, rheumatic or autoimmune diseases, malignancies or metabolic diseases. PATIENT CONCERNS: We present the case of a secondary HLH due to Streptococcus pneumoniae infection in a splenectomised patient for spherocytosis, a 37-year-old patient who was splenectomised in childhood for spherocytosis, without immuneprophylaxis induced by antipneumococcal vaccine. OUTCOMES: He developed a severe pneumococcal sepsis associated with secondary HLH, with unfavorable outcome and death. LESSONS: To our knowledge, just 2 similar cases had been published in the literature, none in which the secondary HLH was the consequence of an invasive pneumococcal infection in a splenectomized patient for spherocytosis, and the association of splenectomy with HLH is surprizin.


title: Chapter Eight Molecular Basis of Coronavirus Virulence and Vaccine Development

text: Abstract Virus vaccines have to be immunogenic, sufficiently stable, safe, and suitable to induce long-lasting immunity. To meet these requirements, vaccine studies need to provide a comprehensive understanding of (i) the protective roles of antiviral B and T-cell-mediated immune responses, (ii) the complexity and plasticity of major viral antigens, and (iii) virus molecular biology and pathogenesis. There are many types of vaccines including subunit vaccines, whole-inactivated virus, vectored, and live-attenuated virus vaccines, each of which featuring specific advantages and limitations. While nonliving virus vaccines have clear advantages in being safe and stable, they may cause side effects and be less efficacious compared to live-attenuated virus vaccines. In most cases, the latter induce long-lasting immunity but they may require special safety measures to prevent reversion to highly virulent viruses following vaccination. The chapter summarizes the recent progress in the development of coronavirus (CoV) vaccines, focusing on two zoonotic CoVs, the severe acute respiratory syndrome CoV (SARS-CoV), and the Middle East respiratory syndrome CoV, both of which cause deadly disease and epidemics in humans. The development of attenuated virus vaccines to combat infections caused by highly pathogenic CoVs was largely based on the identification and characterization of viral virulence proteins that, for example, interfere with the innate and adaptive immune response or are involved in interactions with specific cell types, such as macrophages, dendritic and epithelial cells, and T lymphocytes, thereby modulating antiviral host responses and viral pathogenesis and potentially resulting in deleterious side effects following vaccination.


Molecular characterisation of human coronaviruses from patients with respiratory disease in Slovenia


title: Community-Acquired Respiratory Paramyxovirus Infection After Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience

text: BACKGROUND: Paramyxoviruses include respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (MPV), which may cause significant respiratory tract infectious disease (RTID) and mortality after allogeneic hematopoietic cell transplantation (HCT). However, clinical data regarding frequency and outcome are scarce. METHODS: We identified all paramyxovirus RTIDs in allogeneic HCT recipients diagnosed by multiplex polymerase chain reaction between 2010 and 2014. Baseline characteristics of patients, treatment, and outcome of each episode were analyzed; ie, moderate, severe, and very severe immunodeficiency (verySID) according to HCT ≤6 months, T- or B-cell depletion ≤3 months, graft-versus-host disease, neutropenia, lymphopenia, or hypo-gammaglobulinemia. RESULTS: One hundred three RTID episodes in 66 patients were identified (PIV 47% [48 of 103], RSV 32% [33 of 103], MPV 21% [22 of 103]). Episodes occurred in 85% (87 of 103) at >100 days post-HCT. Lower RTID accounted for 36% (37 of 103). Thirty-nine percent (40 of 103) of RTID episodes required hospitalization and more frequently affected patients with lower RTID. Six percent progressed from upper to lower RTID. Overall mortality was 6% and did not differ between paramyxoviruses. Sixty-one percent (63 of 103) of episodes occurred in patients with SID, and 20.2% (19 of 63) of episodes occurred in patients with verySID. Oral ribavirin plus intravenous immunoglobulin was administered in 38% (39 of 103) of RTIDs, preferably for RSV or MPV (P ≤ .001) and for SID patients (P = .001). Patients with verySID frequently progressed to lower RTID (P = .075), required intensive care unit transfer, and showed higher mortality. CONCLUSION: Paramyxovirus RTID remains a major concern in allogeneic HCT patients fulfilling SID and verySID, emphasizing that efficacious and safe antiviral treatments are urgently needed.


ZIMBABWE: Coronavirus Lockdown


title: Human monoclonal antibodies as candidate therapeutics against emerging viruses

text: The emergence of new pathogens, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Ebola virus, poses serious challenges to global public health and highlights the urgent need for novel antiviral approaches. Monoclonal antibodies (mAbs) have been successfully used to treat various diseases, particularly cancer and immunological disorders. Antigen-specific mAbs have been isolated using several different approaches, including hybridoma, transgenic mice, phage display, yeast display, and single B-cell isolation. Consequently, an increasing number of mAbs, which exhibit high potency against emerging viruses in vitro and in animal models of infection, have been developed. In this paper, we summarize historical trends and recent developments in mAb discovery, compare the advantages and disadvantages of various approaches to mAb production, and discuss the potential use of such strategies for the development of antivirals against emerging diseases. We also review the application of recently developed human mAbs against SARS-CoV, MERS-CoV, and Ebola virus and discuss prospects for the development of mAbs as therapeutic agents against emerging viral diseases.


title: Canine Enteric Coronaviruses: Emerging Viral Pathogens with Distinct Recombinant Spike Proteins

text: Canine enteric coronavirus (CCoV) is an alphacoronavirus infecting dogs that is closely related to enteric coronaviruses of cats and pigs. While CCoV has traditionally caused mild gastro-intestinal clinical signs, there are increasing reports of lethal CCoV infections in dogs, with evidence of both gastrointestinal and systemic viral dissemination. Consequently, CCoV is now considered to be an emerging infectious disease of dogs. In addition to the two known serotypes of CCoV, novel recombinant variants of CCoV have been found containing spike protein N-terminal domains (NTDs) that are closely related to those of feline and porcine strains. The increase in disease severity in dogs and the emergence of novel CCoVs can be attributed to the high level of recombination within the spike gene that can occur during infection by more than one CCoV type in the same host.


Vagueness and Costs of the Pause on Gain-of-Function (GOF) Experiments on Pathogens with Pandemic Potential, Including Influenza Virus


title: Association of COVID-19 pandemic with meteorological parameters over Singapore

text: Abstract Meteorological parameters are the critical factors affecting the transmission of infectious diseases such as Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and influenza. Consequently, infectious disease incidence rates are likely to be influenced by the weather change. This study investigates the role of Singapore's hot tropical weather in COVID-19 transmission by exploring the association between meteorological parameters and the COVID-19 pandemic cases in Singapore. This study uses the secondary data of COVID-19 daily cases from the webpage of Ministry of Health (MOH), Singapore. Spearman and Kendall rank correlation tests were used to investigate the correlation between COVID-19 and meteorological parameters. Temperature, dew point, relative humidity, absolute humidity, and water vapor showed positive significant correlation with COVID-19 pandemic. These results will help the epidemiologists to understand the behavior of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus against meteorological variables. This study finding would be also a useful supplement to help the local healthcare policymakers, Center for Disease Control (CDC), and the World Health Organization (WHO) in the process of strategy making to combat COVID-19 in Singapore.


title: Short report on implications of Covid-19 and emerging zoonotic infectious diseases for pastoralists and Africa

text: Many emerging and re-emerging zoonotic infectious diseases occur in Africa. These are projected to increase as human–animal host contact increases owing to increasing environmental degradation that shrinks nature habitats for wildlife over the continent. The current outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) responsible for causing coronavirus disease in 2019 (COVID-19) has reinvigorated discourse on the disruptiveness of the zoonotic emerging infectious diseases, owing to their transboundary character. Even as the world focuses on the COVID-19 sweeping pandemic, the Middle East respiratory syndrome coronavirus (MERS)-CoV re-emerged in Saudi Arabia infecting 18 people with five deaths; this has barely received any attention. This outbreak is particularly of concern to the pastoralists in the Horn of Africa, a region that has in recent past seen an increase in camel trade with the Gulf States, especially Yemen and Saudi Arabia. Emerging and re-emerging zoonotic infectious diseases are complex, depend on human–animal–environment interaction and pose a strain on public health systems. There is a need to address these diseases dynamically through a synergistic approach, drawing on expertise from diverse sectors. One Health approach has distinguished itself as an integrative action able to bring together multiple actors on a global, national and local scale to advance the attainment of optimal health outcomes for people, animals and the environment. One Health works by strengthening the preparedness, response, mitigation and monitoring of zoonotic infectious disease risks collaboratively. We opine that as zoonotic emerging and re-emerging infectious diseases continue to rise over pastoral Africa, comprehensive implementation of the One Health approach will be urgently required.


title: Epidemic Viral Pneumonia and Other Emerging Pathogens

text: Viruses cause a high percentage of community-acquired pneumonias. The advent of polymerase chain reaction and other molecular techniques has been associated with the detection of a higher prevalence of common respiratory viruses than previously suspected. Better diagnostics have shown new viral pathogens regularly in epidemics, immunocompromised patients, and occasionally children. Despite better diagnostics, treatment for all but influenza is still very limited.


title: Management of infections in critically ill returning travellers in the intensive care unit—I: considerations on infection control and transmission of resistance

text: Summary Depending on their destinations and activities, international travellers are at a significant risk of contracting both communicable and non-communicable diseases. On return to their home countries, such travellers may require intensive care. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and more recently Ebola haemorrhagic fever, has highlighted the risks. Other well-known communicable pathogens such as methicillin-resistant Staphylococcus aureus and carbapenemase-producing Enterobacteriaceae have been described previously. However, malaria remains by far the most important cause of death. The issues related to imported antibiotic resistance and protection from highly contagious diseases are reviewed here. Surveillance strategies based on epidemiological data (country visited, duration of travel, and time elapsed since return) and clinical syndromes, together with systematic search policies, are usually mandatory to limit the risk of an outbreak. Single-bed hospital rooms and isolation according to symptoms should be the rule while awaiting laboratory test results. Because person-to-person contact is the main route of transmission, healthcare workers should implement specific prevention strategies.


title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach

text: The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin converting enzyme-2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.


An adult case of metapneumovirus-induced acute encephalitis


title: Two specific membrane-bound aminopeptidase N isoforms from Aedes aegypti larvae serve as functional receptors for the Bacillus thuringiensis Cry4Ba toxin implicating counterpart specificity

text: Abstract The interaction between Bacillus thuringiensis Cry toxins and their receptors on midgut cells of susceptible insect larvae is the critical determinant in toxin specificity. Besides GPI-linked alkaline phosphatase in Aedes aegypti mosquito-larval midguts, membrane-bound aminopeptidase N (AaeAPN) is widely thought to serve as a Cry4Ba receptor. Here, two full-length AaeAPN isoforms, AaeAPN2778 and AaeAPN2783, predicted to be GPI-linked were cloned and successfully expressed in Spodoptera frugiperda (Sf9) cells as 112- and 107-kDa membrane-bound proteins, respectively. In the cytotoxicity assay, Sf9 cells expressing each of the two AaeAPN isoforms showed increased sensitivity to the Cry4Ba mosquito-active toxin. Double immunolocalization revealed specific binding of Cry4Ba to each individual AaeAPN expressed on the cell membrane surface. Sequence analysis and homology-based modeling placed these two AaeAPNs to the M1 aminopeptidase family as they showed similar four-domain structures, with the most conserved domain II being the catalytic component. Additionally, the most variable domain IV containing negatively charged surface patches observed only in dipteran APNs could be involved in insect specificity. Overall results demonstrated that these two membrane-bound APN isoforms were responsible for mediating Cry4Ba toxicity against AaeAPN-expressed Sf9 cells, suggesting their important role as functional receptors for the toxin counterpart in A. aegypti mosquito larvae.


title: Calprotectin, a new biomarker for diagnosis of acute respiratory infections

text: Respiratory tract infections require early diagnosis and adequate treatment. With the antibiotic overuse and increment in antibiotic resistance there is an increased need to accurately distinguish between bacterial and viral infections. We investigated the diagnostic performance of calprotectin in respiratory tract infections and compared it with the performance of heparin binding protein (HBP) and procalcitonin (PCT). Biomarkers were analyzed in patients with viral respiratory infections and patients with bacterial pneumonia, mycoplasma pneumonia and streptococcal tonsillitis (n = 135). Results were compared with values obtained from 144 healthy controls. All biomarkers were elevated in bacterial and viral infections compared to healthy controls. Calprotectin was significantly increased in patients with bacterial infections; bacterial pneumonia, mycoplasma pneumonia and streptococcal tonsillitis compared with viral infections. PCT was significantly elevated in patients with bacterial pneumonia compared to viral infections but not in streptococcal tonsillitis or mycoplasma caused infections. HBP was not able to distinguish between bacterial and viral causes of infections. The overall clinical performance of calprotectin in the distinction between bacterial and viral respiratory infections, including mycoplasma was greater than performance of PCT and HBP. Rapid determination of calprotectin may improve the management of respiratory tract infections and allow more precise diagnosis and selective use of antibiotics.


title: Scoring systems for predicting mortality for severe patients with COVID-19

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) has been widely spread and caused tens of thousands of deaths, especially in patients with severe COVID-19. This analysis aimed to explore risk factors for mortality of severe COVID-19, and establish a scoring system to predict in-hospital deaths. METHODS: Patients with COVID-19 were retrospectively analyzed and clinical characteristics were compared. LASSO regression as well as multivariable analysis were used to screen variables and establish prediction model. FINDINGS: A total of 2529 patients with COVID-19 was retrospectively analyzed, and 452 eligible severe COVID-19 were used for finally analysis. In training cohort, the median age was 66•0 years while it was 73•0 years in non-survivors. Patients aged 60–75 years accounted for the largest proportion of infected populations and mortality toll. Anti-SARS-CoV-2 antibodies were monitored up to 54 days, and IgG levels reached the highest during 20–30 days. No differences were observed of antibody levels between severe and non-severe patients. About 60.2% of severe patients had complications. Among acute myocardial injury (AMI), acute kidney injury (AKI) and acute liver injury (ALI), the heart was the earliest injured organ, whereas the time from AKI to death was the shortest. Age, diabetes, coronary heart disease (CHD), percentage of lymphocytes (LYM%), procalcitonin (PCT), serum urea, C reactive protein and D-dimer (DD), were identified associated with mortality by LASSO binary logistic regression. Then multivariable analysis was performed to conclude that old age, CHD, LYM%, PCT and DD remained independent risk factors for mortality. Based on the above variables, a scoring system of COVID-19 (CSS) was established to divide patients into low-risk and high-risk groups. This model displayed good discrimination (AUC=0·919) and calibration (P=0·264). Complications in low-risk and high-risk groups were significantly different (P<0·05). Use of corticosteroids in low-risk groups increased hospital stays by 4·5 days (P=0·036) and durations of disease by 7·5 days (P=0·012) compared with no corticosteroids. INTERPRETATION: Old age, CHD, LYM%, PCT and DD were independently related to mortality. CSS was useful for predicting in-hospital mortality and complications, and it could help clinicians to identify high-risk patients with poor prognosis. FUNDING: This work was supported by the Key Project for Anti-2019 novel Coronavirus Pneumonia from the Ministry of Science and Technology, China (grant number 2020YFC0845500).


title: CT manifestations of coronavirus disease-2019: A retrospective analysis of 73 cases by disease severity

text: Abstract Purpose To report CT features of coronavirus disease-2019 (COVID-19) in patients with various disease severity. Methods The CT manifestations and clinical data of 73 patients with COVID-19 were retrospectively collected in 6 hospitals from Jan 21 to Feb 3, 2020. We analyzed the initial and follow-up CT features of patients with disease severity, according to the Guidelines for the Diagnosis and Treatment of New Coronavirus Pneumonia. Results Six patients (8%) were diagnosed as mild type pneumonia; these patients had no obvious abnormal CT findings or manifested mild changes of lung infection. All 43 patients (59 %) with common type presented unique or multiple ground-glass opacities (GGO) in the periphery of the lungs, with or without interlobular septal thickening. In the 21 patients (29 %) with severe type, extensive GGO and pulmonary consolidation were found in 16 cases (16/21, 76 %) and 5 cases (24 %), respectively. An extensive "white lung", with atelectasis and pleural effusion were found in critical type patients (3, 4%). On the resolutive phase of the disease, CT abnormalities showed complete resolution, or demonstrated residual linear opacities. Conclusions Different CT features are seen according to disease severity, which can help COVID-19 stratification.


title: Low rate of severe acute respiratory syndrome coronavirus 2 spread among health-care personnel using ordinary personal protection equipment in a medium-incidence setting

text: [Figure: see text]


title: Validity and reliability of the proposed core competency for infection control nurses of hospitals in Hong Kong

text: Literature review and the Delphi approach were used to draft the core competency items of hospital infection control nurses in Hong Kong. Content validity, internal consistency, and test-retest reliability of the proposed core competency were ensured. The result serves as the foundation of developing training and assessment tools for infection control nurses in Hong Kong.


title: ACE2 correlated with immune infiltration serves as a prognostic biomarker in endometrial carcinoma and renal papillary cell carcinoma: implication for COVID-19

text: Angiotensin-converting enzyme 2 (ACE2) is a member of the renin-angiotension system, however, the correlation between ACE2 and prognosis in UCEC (Uterine Corpus Endometrial Carcinoma) and KIRP (Kidney Renal Papillary Cell Carcinoma) is not clear. We analyzed the expression levels of ACE2 in the Oncomine and TIMER databases, the correlation between ACE2 and overall survival in the PrognoScan, GEPIA and Kaplan-Meier plotter databases. The correlation between ACE2 and immune infiltration level and the type markers of immune cells was investigated in TIMER database. A prognosis analysis based on the expression levels of ACE2 was further performed in related immune cells subgroup. The ACE2 promoter methylation profile was tested in the UALCAN database. In addition, we used GSE30589 and GSE52920 databases to elucidate the changes of ACE2 expression in vivo and in vitro after SARS-CoV infection. ACE2 was elevated in UCEC and KIRP, and high ACE2 had a favorable prognosis. The expression of ACE2 was positively correlated with the level of immune infiltration of macrophage in KIRP, B cell, CD4+T cell, neutrophil and dendritic cell immune infiltration levels in UCEC. ACE2 was significantly positively correlated with the type markers of B cells and neutrophils, macrophages in UCEC, while ACE2 in KIRP was positively correlated with the type markers of macrophages. High ACE2 expression level had a favorable prognosis in different enriched immune cells subgroups in UCEC and KIRP. And the promoter methylation levels of ACE2 in UCEC and KIRP were significantly reduced. What’s more, we found that the expression of ACE2 decreased in vivo and in vitro after SARS-CoV infection. In conclusion, ACE2 expression increased significantly in UCEC and KIRP, elevated ACE2 was positively correlated with immune infiltration and prognosis. Moreover, tumor tissues may be more susceptible to SARS-CoV-2 infection in COVID-19 patients with UCEC and KIRP, which may worsen the prognosis.


title: Host genes regulate transcription of sperm-introduced hepatitis B virus genes in embryo

text: Abstract Hepatitis B virus (HBV) can invade the male germline, and sperm-introduced HBV genes could be transcribed in embryo. This study was to explore whether viral gene transcription is regulated by host genes. Embryos were produced by in vitro fertilization of hamster oocytes with human sperm containing the HBV genome. Total RNA extracted from test and control embryos were subjected to SMART-PCR, SSH, microarray hybridization, sequencing and BLAST analysis. Twenty-nine sequences showing significant identity to five human gene families were identified, with CSH2, EIF4G2, PCBD2, PSG4 and TTN selected to represent target genes. Using qRT-PCR, when CSH2 and PCBD2 (or EIF4G2, PSG4 and TTN) were silenced by RNAi, transcriptional levels of HBV s and x genes decreased (or increased). This is the first report that host genes participate in regulation of sperm-introduced HBV gene transcription in embryo, which is critical to prevent negative impact of HBV infection on early embryonic development.


title: Synthesis and characterization of different immunogenic viral nanoconstructs from rotavirus VP6 inner capsid protein

text: In order to deliver low-cost viral capsomeres from a large amount of soluble viral VP6 protein from human rotavirus, we developed and optimized a biotechnological platform in Escherichia coli. Specifically, three different expression protocols were compared, differing in their genetic constructs, ie, a simple native histidine-tagged VP6 sequence, VP6 fused to thioredoxin, and VP6 obtained with the newly described small ubiquitin-like modifier (SUMO) fusion system. Our results demonstrate that the histidine-tagged protein does not escape the accumulation in the inclusion bodies, and that SUMO is largely superior to the thioredoxin-fusion tag in enhancing the expression and solubility of VP6 protein. Moreover, the VP6 protein produced according to the SUMO fusion tag displays well-known assembly properties, as observed in both transmission electron microscopy and atomic force microscopy images, giving rise to either VP6 trimers, 60 nm spherical virus-like particles, or nanotubes a few microns long. This different quaternary organization of VP6 shows a higher level of immunogenicity for the elongated structures with respect to the spheres or the protein trimers. Therefore, the expression and purification strategy presented here – providing a large amount of the viral capsid protein in the native form with relatively simple, rapid, and economical procedures – opens a new route toward large-scale production of a more efficient antigenic compound to be used as a vaccination tool or as an adjuvant, and also represents a top-quality biomaterial to be further modified for biotechnological purposes.


title: Severe Acute Respiratory Syndrome and Coronavirus

text: Severe acute respiratory syndrome (SARS) is a highly infectious disease with a significant morbidity and mortality. Respiratory failure is the major complication, and patients may progress to acute respiratory distress syndrome. Health care workers are particularly vulnerable to SARS. SARS has the potential of being converted from droplet to airborne transmission. There is currently no proven effective treatment of SARS, so early recognition, isolation, and stringent infection control are the key to controlling this highly contagious disease. Horseshoe bats are implicated in the emergence of novel coronavirus infection in humans. Further studies are needed to examine host genetic markers that may predict clinical outcome.


title: Validation of a clinical scoring system for bovine respiratory disease complex diagnosis in preweaned dairy calves using a Bayesian framework

text: Abstract Bovine respiratory disease complex is a major cause of illness in dairy calves. The diagnosis of active infection of the lower respiratory tract is challenging on daily basis in the absence of accurate clinical signs. Clinical scoring systems such as the Californian scoring system, are appealing but were developed without considering the imperfection of reference standard tests used for case definition. This study used a Bayesian latent class model to update Californian prediction rules. The results of clinical examination and ultrasound findings of 608 preweaned dairy calves were used. A model accounting for imperfect accuracy of thoracic ultrasound examination was used to obtain updated weights for the clinical signs included in the Californian scoring system. There were 20 points (95% Bayesian credible intervals: 11–29) for abnormal breathing pattern, 16 points (95% BCI: 4–29) for ear drop/head tilt, 16 points (95% BCI: 9–25) for cough, 10 points (95% BCI: 3–18) for the presence of nasal discharge, 7 points (95% BCI: −1 to 8) for rectal temperature ≥39.2 °C, and −1 points (95% BCI: −9 to 8) for the presence of ocular discharge. The optimal cut-offs were determined using the misclassification cost-term term (MCT) approach with different possible scenarios of expected prevalence and different plausible ratio of false negative costs/false positive costs. The predicted probabilities of active infection of the lower respiratory tract were also obtained using posterior densities of the main logistic regression model. Depending on the context, cut-off varying from 9 to 16 can minimized the MCT. The optimal cut-off decreased when expected prevalence of disease and false negative/false positive ratio increased.


title: Improvement in Mortality and End-Stage Renal Disease in Patients With Type 2 Diabetes After Acute Kidney Injury Who Are Prescribed Dipeptidyl Peptidase-4 Inhibitors

text: Abstract Objective To focus on the potential beneficial effects of the pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP4is) on attenuating progression of diabetic kidney disease in reducing the long-term effect of the acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Patients and Methods Data from the National Health Insurance Research Database from January 1, 1999, to July 31, 2011, were analyzed, and patients with diabetes weaning from dialysis-requiring AKI were identified. Cox proportional hazards models and inverse-weighted estimates of the probability of treatment were used to adjust for treatment selection bias. The outcomes were incident end-stage renal disease (ESRD) and mortality, major adverse cardiovascular events, and hospitalized heart failure. Results Of a total of 6165 patients with diabetes weaning from dialysis-requiring AKI identified, 5635 (91.4%) patients were DPP4i nonusers and 530 (8.6%) patients were DPP4i users. Compared with DPP4i nonusers, DPP4i users had a lower risk of ESRD (hazard ratio, 0.81; 95% CI, 0.70-0.94; P=.04) and all-cause mortality (hazard ratio, 0.28; 95% CI, 0.23-0.34; P<.001) after adjustments for CKD, advanced CKD, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use. In contrast, the risk of major adverse cardiovascular events and hospitalized heart failure did not differ significantly between groups. Conclusion Dipeptidyl peptidase-4 inhibitor users had a lower risk of ESRD and mortality than did nonusers among patients with diabetes after weaning from dialysis-requiring AKI. Therefore, a prospective study of AKI to CKD transitions after episodes of AKI is needed to optimally target DPP4i interventions.


title: Identification of potential inhibitors of three key enzymes of SARS-CoV2 using computational approach

text: The recent outbreak of coronavirus disease-19 (COVID-19) continues to drastically affect healthcare throughout the world. To date, no approved treatment regimen or vaccine is available to effectively attenuate or prevent the infection. Therefore, collective and multidisciplinary efforts are needed to identify new therapeutics or to explore effectiveness of existing drugs and drug-like small molecules against SARS-CoV-2 for lead identification and repurposing prospects. This study addresses the identification of small molecules that specifically bind to any of the three essential proteins (RdRp, 3CL-protease and helicase) of SARS-CoV-2. By applying computational approaches we screened a library of 4574 compounds also containing FDA-approved drugs against these viral proteins. Shortlisted hits from initial screening were subjected to iterative docking with the respective proteins. Ranking score on the basis of binding energy, clustering score, shape complementarity and functional significance of the binding pocket was applied to identify the binding compounds. Finally, to minimize chances of false positives, we performed docking of the identified molecules with 100 irrelevant proteins of diverse classes thereby ruling out the non-specific binding. Three FDA-approved drugs showed binding to 3CL-protease either at the catalytic pocket or at an allosteric site related to functionally important dimer formation. A drug-like molecule showed binding to RdRp in its catalytic pocket blocking the key catalytic residues. Two other drug-like molecules showed specific interactions with helicase at a key domain involved in catalysis. This study provides lead drugs or drug-like molecules for further in vitro and clinical investigation for drug repurposing and new drug development prospects.


title: The Interplay of Viral and Host Factors in Chikungunya Virus Infection: Targets for Antiviral Strategies

text: Chikungunya virus (CHIKV) has re-emerged as one of the many medically important arboviruses that have spread rampantly across the world in the past decade. Infected patients come down with acute fever and rashes, and a portion of them suffer from both acute and chronic arthralgia. Currently, there are no targeted therapeutics against this debilitating virus. One approach to develop potential therapeutics is by understanding the viral-host interactions. However, to date, there has been limited research undertaken in this area. In this review, we attempt to briefly describe and update the functions of the different CHIKV proteins and their respective interacting host partners. In addition, we also survey the literature for other reported host factors and pathways involved during CHIKV infection. There is a pressing need for an in-depth understanding of the interaction between the host environment and CHIKV in order to generate potential therapeutics.


title: Etoposid-based therapy for severe forms of COVID-19

text: Abstract The new coronavirus infection COVID-19 has quickly become a global health emergency. Mortality is principally due to severe Acute Respiratory Distress Syndrome (ARDS) which relays only on supportive treatment. Numerous pathological, clinical and laboratory findings rise the similarity between moderate to severe COVID-19 and haemophagocytic lymphohistiocytosis (HLH). Etoposide-based protocol including dexametasone is the standard of care for secondary HLH. The protocol has been successfully used in HLHs that are secondary to EBV and H1N1 infections by inducing complete response and pronged survival. These observations prompt to consider this cytotoxic therapy in HLH associated to moderately severe to severe forms of COVID-19.


title: Rapid differentiation of PEDV wild-type strains and classical attenuated vaccine strains by fluorescent probe-based reverse transcription recombinase polymerase amplification assay

text: BACKGROUND: Porcine epidemic diarrhea virus (PEDV), an intestinal coronavirus that causes acute diarrhea and high mortality in suckling piglets, can result in high economic losses in the swine industry. In recent years, despite the use of China’s current vaccine immunization strategy, multiple types of PEDV strains were still found in immunized swine herds. Our research aims to explore a new rapid differentiation method to distinguish the different types of PEDV strains and assess the safety evaluation of classical attenuated vaccine strains in swine herds. RESULTS: In the study, a differential one-step quantitative real-time fluorescent reverse transcription recombinase polymerase amplification (real-time RT-RPA) method based on the PEDV universal real-time RT-RPA assay was established according to the ORF1 deletion sequences of three classical attenuated vaccine strains (PEDV attenuated vaccine KC189944, attenuated CV777 and DR13) and five Vero cell-adapted isolates (JS2008, SDM, SQ2014, SC1402, HLJBY), which could effectively differentiate PEDV classical attenuated vaccine strains from wild-type strains (PEDV classical wild strains and variant strains). The detection limits of PEDV RNA in the both PEDV real-time RT-RPA assays were 300 copies within 20 min at 39 °C, and the detection limits of classical attenuated vaccine strain CV777, Vero-cell-adapted isolate JS2008, and PEDV wild-type strain DX were 10(0.5) TCID(50)/100 μL, 10(1.1) TCID(50)/100 μL, and 10(1.2) TCID(50)/100 μL, respectively. Both assays were highly specific for PEDV, showing no cross-reactivity with other enteral viruses. CONCLUSION: This RPA method we developed is simple, time-effective, and safe and provides a reliable technical tool for the differential diagnosis and clinical epidemic surveillance of PEDV classical attenuated vaccine strains and wild-type strains.


title: Dynamic evolution of COVID-19 on chest computed tomography: experience from Jiangsu Province of China

text: OBJECTIVES: To determine the patterns of chest computed tomography (CT) evolution according to disease severity in a large coronavirus disease 2019 (COVID-19) cohort in Jiangsu Province, China. METHODS: This retrospective cohort study was conducted from January 10, 2020, to February 18, 2020. All patients diagnosed with COVID-19 in Jiangsu Province were included, retrospectively. Quantitative CT measurements of pulmonary opacities including volume, density, and location were extracted by deep learning algorithm. Dynamic evolution of these measurements was investigated from symptom onset (day 1) to beyond day 15. Comparison was made between severity groups. RESULTS: A total of 484 patients (median age of 47 years, interquartile range 33–57) with 954 CT examinations were included, and each was assigned to one of the three groups: asymptomatic/mild (n = 63), moderate (n = 378), severe/critically ill (n = 43). Time series showed different evolution patterns of CT measurements in the groups. Following disease onset, posteroinferior subpleural area of the lung was the most common location for pulmonary opacities. Opacity volume continued to increase beyond 15 days in the severe/critically ill group, compared with peaking on days 13–15 in the moderate group. Asymptomatic/mild group had the lowest opacity volume which almost resolved after 15 days. The opacity density began to drop from day 10 to day 12 for moderately ill patients. CONCLUSIONS: Volume, density, and location of the pulmonary opacity and their evolution on CT varied with disease severity in COVID-19. These findings are valuable in understanding the nature of the disease and monitoring the patient’s condition during the course of illness. KEY POINTS: • Volume, density, and location of the pulmonary opacity on CT change over time in COVID-19. • The evolution of CT appearance follows specific pattern, varying with disease severity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00330-020-06976-6) contains supplementary material, which is available to authorized users.


title: Practical strategies for a safe and effective delivery of aerosolized medications to patients with COVID-19

text: Abstract The COVID-19, the disease caused by a novel coronavirus and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly across the globe. It has caused outbreaks of illness due to person-to-person transmission of the virus mainly via close contacts and droplets produced by an infected person's cough or sneeze. Exhaled droplets from infected patients with COVID-19 can be inhaled into the lungs and leads to respiratory illness such as pneumonia and acute respiratory distress syndrome. Although aerosol therapy is a mainstay procedure used to treat pulmonary diseases at home and healthcare settings, it has a potential for fugitive emissions during therapy due to the generation of aerosols and droplets as a source of respiratory pathogens. Delivering aerosolized medications to patients with COVID-19 can aggravate the spread of the novel coronavirus. This has been a real concern for caregivers and healthcare professionals who are susceptible to unintended inhalation of fugitive emissions during therapy. Due to a scarcity of information in this area of clinical practice, the purpose of this paper is to explain how to deliver aerosolized medications to mild-, sub-intensive, and intensive patients with COVID-19 and how to protect staff from exposure to exhaled droplets during aerosol therapy.


title: Survey for selected pathogens in wild pigs (Sus scrofa) from Guam, Marianna Islands, USA

text: Abstract Pigs (Sus scrofa) were introduced to Guam in the 1600’s and are now present in high densities throughout the island. Wild pigs are reservoirs for pathogens of concern to domestic animals and humans. Exposure to porcine parvovirus, transmissible gastroenteritis, and Leptospira interrogans has been documented in domestic swine but data from wild pigs are lacking. The close proximity of humans, domestic animals, and wild pigs, combined with the liberal hunting of wild pigs, results in frequent opportunities for pathogen transmission. From February–March 2015, blood, tissue and ectoparasite samples were collected from 47 wild pigs. Serologic testing found exposure to Brucella spp. (2%), Toxoplasma gondii (11%), porcine reproductive and respiratory syndrome (PRRS) virus (13%), porcine circovirus type 2 (36%), pseudorabies virus (64%), Actinobacillus pleuropneumoniae (93%), Lawsonia intracellularis (93%), and porcine parvovirus (94%). Eleven (24%) samples had low titers (1:100) to Leptospira interrogans serovars Bratislava (n=6), Icterohaemorrhagiae (n=6), Pomona (n=2), and Hardjo (n=1). Kidney samples from nine pigs with Leptospira antibodies were negative for Leptospira antigens. Numerous pigs had Metastrongylus lungworms and three had Stephanurus dentatus. Lice (Hematopinus suis) and ticks (Amblyomma breviscutatum) were also detected. No antibodies to Influenza A viruses were detected. In contrast to the previous domestic swine survey, we found evidence of numerous pathogens in wild pigs including new reports of pseudorabies virus, PRRS virus, Brucella, and Leptospira in pigs on Guam. These findings highlight that domestic swine-wild pig interactions should be prevented and precautions are needed when handling wild pigs to minimize the risk of pathogen transmission.


title: Risk of zoonotic transmission of HEV from rabbits

text: Abstract Hepatitis E virus strains from rabbits indicate that these mammals may be a reservoir for HEVs that cause infection in humans. Further issues remain to be clarified, including whether the genotype of rabbit HEV differs from human and swine HEV genotype 3 and whether rabbit HEV can infect human and other animals. HEV was found in farmed rabbits in several geographic areas of China, in USA and more recently in France. The prevalence of antibodies against HEV was 36%, 57% and 55% in rabbits from Virginia (USA), Gansu Province and Beijing (China), respectively. HEV RNA was detected in 16.5% of serum samples from farmed rabbits in Virginia, 7.5% in Gansu Province and 7.0% in Beijing. HEV RNA was detected in 7% of bile samples from farmed rabbits and in 23% of liver samples from wild rabbits in France. The full-length genomic sequences analysis indicates that all the rabbit strains belong to the same clade. Nucleotide sequences were 72.2–78.2% identical to HEV genotypes 1–4. Comparison with HEV sequences of human strains circulating in France and reference sequences identified a human strain closely related to rabbit HEV. A 93-nucleotide insertion in the X domain of the ORF1 of the human strain and in all the rabbit HEV strains was found. Moreover, the ability of rabbit HEV to cause cross-species infection in a pig model has recently been demonstrated. Rabbit HEV can replicate efficiently in human cell lines. Collectively, these data support the possibility of zoonotic transmission of HEV from rabbits.


title: Coronaviruses — drug discovery and therapeutic options

text: In humans, infections with the human coronavirus (HCoV) strains HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 usually result in mild, self-limiting upper respiratory tract infections, such as the common cold. By contrast, the CoVs responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which were discovered in Hong Kong, China, in 2003, and in Saudi Arabia in 2012, respectively, have received global attention over the past 12 years owing to their ability to cause community and health-care-associated outbreaks of severe infections in human populations. These two viruses pose major challenges to clinical management because there are no specific antiviral drugs available. In this Review, we summarize the epidemiology, virology, clinical features and current treatment strategies of SARS and MERS, and discuss the discovery and development of new virus-based and host-based therapeutic options for CoV infections. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrd.2015.37) contains supplementary material, which is available to authorized users.


title: Exercise-induced immune system response: Anti-inflammatory status on peripheral and central organs

text: Abstract A wide array of molecular pathways has been investigated during the past decade in order to understand the mechanisms by which the practice of physical exercise promotes neuroprotection and reduces the risk of developing communicable and non-communicable chronic diseases. While a single session of physical exercise may induce a transient imbalance of cell homeostasis, repeated physical exercise sessions will improve immunosurveillance and immunocompetence. Additionally, immune cells from the central nervous system will acquire an anti-inflammatory phenotype, protecting central functions from age-induced cognitive decline. This review highlights the exercise-induced anti-inflammatory effect on the prevention or treatment of common chronic clinical and experimental settings. It also suggests the use of pterins in biological fluids as sensitive biomarkers to follow the anti-inflammatory effect of physical exercise.


title: Cómo reestructurar una Sección de Medicina Fetal en tiempos de pandemia COVID-19. Medidas de seguridad y limpieza de los equipos ecográficos

text: Resumen En situación de pandemia, los tres principios básicos en la atención sanitaria son priorizar los recursos, mantener el confinamiento del paciente para evitar la transmisión comunitaria y el colapso sanitario y reducir la asistencia no prioritaria con el fin de evitar la exposición del paciente y de salvaguardar la salud del profesional sanitario. El control antenatal debe mantenerse durante el periodo de crisis sanitaria, independientemente del estado de alerta COVID-19. La ecografía obstétrica en una prueba fundamental para la toma de decisiones clínicas durante el embarazo, con un impacto en el manejo del binomio madre-feto y en el resultado perinatal, por lo que se ha de garantizar su realización. Con el fin de reducir las visitas presenciales al mínimo número posible, estas se intentarán organizar teniendo en cuenta los controles ecográficos establecidos. Basados en la evidencia científica y en las principales guías nacionales e internacionales, hemos elaborado este documento que incluye las principales recomendaciones para el cuidado antenatal de la gestante en el contexto de la pandemia por SARS-CoV-2. En él se recoge cómo debe reestructurarse una Sección de Medicina Fetal ante esta nueva situación, qué medidas de seguridad deben seguirse para la realización de las exploraciones ecográficas y técnicas invasivas y de qué modo debe procederse para la limpieza y desinfección de los equipos ecográficos. Estas recomendaciones deberán adaptarse a los diferentes medios teniendo en cuenta la infraestructura del centro y sus recursos. Abstract During a pandemic, the three basic principles are; to prioritise medical resources, ensure patient lockdown in order to avoid community transmission and prevent healthcare collapse, and keep the number of visits to an absolute minimum to avoid patient exposure and safeguard healthcare workers. Antenatal care must be maintained during a health crisis, regardless of the COVID-19 state of alert. Routine and specialist obstetric ultrasound scans are essential for clinical decision-making during pregnancy, as it has a direct impact on the management of mothers and the foetuses and on the perinatal outcome. In an attempt to minimise in-person visits, these will be organised according to the established ultrasound schedule. Based on scientific evidence, and on existing main national and international guidelines, this document has been prepared, in which proposals and options are provided for managing pregnant women in the context of the SARS-CoV-2 pandemic. It includes measured for how a Foetal Medicine Unit in this health crisis should be restructured, the safety measures that should be followed in the performance of obstetric scans and invasive procedures, and how the ultrasound rooms, equipment, and transducers, should be cleaned and disinfected. These recommendations should be adapted to different units, based on their resources and infrastructure.


title: Twenty-Five Years of Progress in Understanding Major Infectious Diseases of Dairy Cattle

text: Abstract Disease, whether it occurs in cats, cattle, caribou, or other species, is the manifestation of insult to the structural or functional integrity of the living being. Infection may occur with or without evidence of disease. Disease may represent only the “tip of the iceberg” of infection. Prevalence of disease is the proportion of a defined population that meets specific criteria at a point in time, and incidence refers to the proportion of a defined population in which the onset occurs during a specifiable interval. Risk is an instantaneous rate of incidence. Prevalence, incidence, and risk in infectious diseases are quantitative inferences derived from assessment of implications — caveats derived from variables that often are elusive, such as antibiotic resistance to plasmid mediated determinants transferable between species of enteric bacteria, or such as increases in population density among insect vectors influenced by climatic conditions favorable to the insects. Carefully orchestrated manipulation of the etiologic agent or the host response is made possible by ever-expanding understanding of the molecular biology of pathogenicity on the one hand and cellular and humoral immunity on the other. Such understanding often leads to new caveats or destroys old ones based on incomplete information. This paper deals with a selected limited number of infectious diseases of dairy cattle. Knowledge developed around the cited parameters in 13 infectious diseases during the past quarter century is brought into focus. Ten geographically dispersed specialists in infectious diseases of cattle were asked to identify priorities among the array of transmissible diseases important to North America. Except for the mastitis syndrome, which will be given special attention elsewhere in these anniversary papers, the diseases discussed are those wherein major advances in knowledge or major needs for advanced knowledge were of special importance.


title: Enhanced protection in mice induced by immunization with inactivated whole viruses compare to spike protein of middle east respiratory syndrome coronavirus

text: The persistent public health threat of infection with Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the need for an effective and safe MERS-CoV vaccine. In this study, we prepared and vaccinated mice with either a Spike (S) protein or inactivated whole MERS-CoV (IV) with a combined adjuvant (alum+CpG) as a vaccine formulation. Similar levels of the anti-S protein IgG response and neutralizing activity were induced by both the S protein and IV vaccines. In addition, immune responses against three other structural proteins, the envelope (E), membrane (M), and nucleocapsid (N) proteins, were also detected in sera of mice that received IV. No antigen-specific T-cell immunity was detected after vaccination based on the interferon-γ ELISpot assay. Mice were transduced with Ad5-hDPP4 after the final immunization and were then challenged with MERS-CoV (1 × 10(5) plaque-forming units). Compared with the control group (adjuvant alone), mice immunized with the S protein or IV showed slightly lower pathological damage in the lung, as well as reduced antigen expression and lung virus titers. Mice that received IV formulations also showed increased protective immunity (almost no live virus was isolated from the lung). In conclusion, our data indicate that immunization with our IV formulation induced enhanced protection in mice compared to immunization with the S protein against MERS-CoV, which should be further tested in camels and clinical trials.


title: Structural basis for the recognition of the 2019-nCoV by human ACE2

text: Angiotensin-converting enzyme 2 (ACE2) has been suggested to be the cellular receptor for the new coronavirus (2019-nCoV) that is causing the coronavirus disease 2019 (COVID-19). Like other coronaviruses such as the SARS-CoV, the 2019-nCoV uses the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) to engage ACE2. We most recently determined the structure of the full-length human ACE2 in complex with a neutral amino acid transporter B0AT1. Here we report the cryo-EM structure of the full-length human ACE2 bound to the RBD of the 2019-nCoV at an overall resolution of 2.9 Å in the presence of B0AT1. The local resolution at the ACE2-RBD interface is 3.5 Å, allowing analysis of the detailed interactions between the RBD and the receptor. Similar to that for the SARS-CoV, the RBD of the 2019-nCoV is recognized by the extracellular peptidase domain (PD) of ACE2 mainly through polar residues. Pairwise comparison reveals a number of variations that may determine the different affinities between ACE2 and the RBDs from these two related viruses.


title: Coinfections of the Respiratory Tract: Viral Competition for Resources

text: Studies have shown that simultaneous infection of the respiratory tract with at least two viruses is common in hospitalized patients, although it is not clear whether these infections are more or less severe than single virus infections. We use a mathematical model to study the dynamics of viral coinfection of the respiratory tract in an effort to understand the kinetics of these infections. Specifically, we use our model to investigate coinfections of influenza, respiratory syncytial virus, rhinovirus, parainfluenza virus, and human metapneumovirus. Our study shows that during coinfections, one virus can block another simply by being the first to infect the available host cells; there is no need for viral interference through immune response interactions. We use the model to calculate the duration of detectable coinfection and examine how it varies as initial viral dose and time of infection are varied. We find that rhinovirus, the fastest-growing virus, reduces replication of the remaining viruses during a coinfection, while parainfluenza virus, the slowest-growing virus is suppressed in the presence of other viruses.


title: Mucosal Immune System of Cattle All Immune Responses Begin Here

text: This article discusses key concepts important for mucosal immunity. The mucosa is the largest immune organ of the body. The mucosal barrier (the tight junctions and the “kill zone”) along with the mucosa epithelial cells maintaining an anti-inflammatory state are essential for the mucosal firewall. The microbiome (the microorganisms that are in the gastrointestinal, respiratory, and reproductive tract) is essential for immune development, homeostasis, immune response, and maximizing animal productivity. Mucosal vaccination provides an opportunity to protect animals from most infectious diseases because oral, gastrointestinal, respiratory, and reproductive mucosa are the main portals of entry for infectious disease.


title: Epidemiological and clinical differences between sexes and pathogens in a three-year surveillance of acute infectious gastroenteritis in Shanghai

text: Acute infectious gastroenteritis cases in Shanghai, reported over three years, were analyzed. Pathogens were identified in 1031 patients; of these, 725 and 306 were bacterial and viral cases, respectively. Vibrio parahemolyticus and Salmonella were the dominant bacteria, and Caliciviridae and Reoviridae were the dominant viral families in the local area. The acute gastroenteritis epidemic peaks appeared in August and January, which represented the active peak periods of bacteria and viruses, respectively. Logistic regression analyses with sex stratification showed that abdominal pain, fever and ingestion of unsafe food at restaurants were independent factors more frequently associated with bacterial gastroenteritis irrespective of sex; red cell-positive fecal matter was associated with bacterial gastroenteritis with an odds ratio (OR) of 3.28 only in males; and white blood cell count was associated with bacterial gastroenteritis with an OR of 1.02 only in females. Pathogen stratification showed that age, vomiting and red cell-positive fecal matter were associated with males with ORs of 0.99, 0.61 and 1.71, respectively, in bacterial gastroenteritis; and the migrant ratio was higher in males with an OR of 2.29 only in viral gastroenteritis. In conclusion, although bacterial and viral gastroenteritis shared many features, epidemiological and clinical factors differed between sexes and pathogens.


title: Vδ2 T-Cells Kill ZIKV-Infected Cells by NKG2D-Mediated Cytotoxicity

text: An expansion of effector/activated Vδ2 T-cells was recently described in acute Zika virus (ZIKV)-infected patients, but their role in the protective immune response was not clarified. The aim of this study was to define the antiviral activity of Vδ2 T-cells against ZIKV-infected cells. The Vδ2 T-cells expansion and their cytotoxic activity against ZIKV-infected cells were tested in vitro and analyzed by RT-PCR and flow cytometry. We found that ZIKV infection was able to induce Vδ2 T-cells expansion and sensitized A549 cells to Vδ2-mediated killing. Indeed, expanded Vδ2 T-cells killed ZIKV-infected cells through degranulation and perforin release. Moreover, ZIKV infection was able to increase the expression on A549 cells of NKG2D ligands (NKG2DLs), namely MICA, MICB, and ULBP2, at both the mRNA and protein levels, suggesting the possible involvement of these molecules in the recognition by NKG2D-expressing Vδ2 T-cells. Indeed, the killing of ZIKV-infected cells by expanded Vδ2 T-cells was mediated by NKG2D/NKG2DL interaction as NKG2D neutralization abrogated Vδ2 cytotoxicity. Our data showed a strong antiviral activity of Vδ2 T-cells against ZIKV-infected cells, suggesting their involvement in the protective immune response. Other studies are necessary to investigate whether the lack of Vδ2 T-cells expansion in vivo may be associated with disease complications.


title: Taking control amidst the chaos: Emotion regulation during the COVID-19 pandemic

text: Abstract The COVID-19 pandemic represents a major global health crisis that continues to threaten public health and safety. Although the pandemic is still unfolding, measures to reduce the spread of the virus have spawned significant challenges to people's current work as well as their careers more generally. In this commentary, we discuss the implications of COVID-19 for maintaining one's psychological well-being and employment security, and also managing family and work responsibilities. We also bring forth evidence from the emotion regulation literature to help mitigate the downstream negative consequences of COVID-19 on people's work lives. Finally, we offer several suggestions for future scholarly investigation into how this pandemic impacts vocational behavior.


title: Heparin – an old drug with multiple potential targets in Covid‐19 therapy

text: A prominent clinical feature of severe Covid‐19 infection is respiratory failure associated with pulmonary coagulopathy. Recent reports published in Thrombosis and Haemostasis show that treatment with low‐molecular weight heparin (LMWH) decreases mortality in critically ill patients with sepsis‐induced hypercoagulation, and thus argue for prophylactic administration of the anticoagulant. In addition, the authors point to non‐anticoagulant activities of heparin, in particular anti‐inflammatory effects with potential to prevent deterioration of the disease. We would like to use this opportunity to clarify the biochemical background of the diverse activities of heparin, and further, how this information may be exploited to generate more efficient treatment of the viral infection. Mechanisms to consider relate to the functional roles of proteins interacting with heparan sulfate (HS), a polysaccharide closely related to heparin.


title: Influenza-Like Illness Sentinel Surveillance in Peru

text: BACKGROUND: Acute respiratory illnesses and influenza-like illnesses (ILI) are a significant source of morbidity and mortality worldwide. Despite the public health importance, little is known about the etiology of these acute respiratory illnesses in many regions of South America. In 2006, the Peruvian Ministry of Health (MoH) and the US Naval Medical Research Center Detachment (NMRCD) initiated a collaboration to characterize the viral agents associated with ILI and to describe the clinical and epidemiological presentation of the affected population. METHODOLOGY/PRINCIPAL FINDINGS: Patients with ILI (fever ≥38°C and cough or sore throat) were evaluated in clinics and hospitals in 13 Peruvian cities representative of the four main regions of the country. Nasal and oropharyngeal swabs, as well as epidemiological and demographic data, were collected from each patient. During the two years of this study (June 2006 through May 2008), a total of 6,835 patients, with a median age of 13 years, were recruited from 31 clinics and hospitals; 6,308 were enrolled by regular passive surveillance and 527 were enrolled as part of outbreak investigations. At least one respiratory virus was isolated from the specimens of 2,688 (42.6%) patients, with etiologies varying by age and geographical region. Overall the most common viral agents isolated were influenza A virus (25.1%), influenza B virus (9.7%), parainfluenza viruses 1, 2, and 3, (HPIV-1,-2,-3; 3.2%), herpes simplex virus (HSV; 2.6%), and adenoviruses (1.8%). Genetic analyses of influenza virus isolates demonstrated that three lineages of influenza A H1N1, one lineage of influenza A H3N2, and two lineages of influenza B were circulating in Peru during the course of this study. CONCLUSIONS: To our knowledge this is the most comprehensive study to date of the etiologic agents associated with ILI in Peru. These results demonstrate that a wide range of respiratory pathogens are circulating in Peru and this fact needs to be considered by clinicians when treating patients reporting with ILI. Furthermore, these data have implications for influenza vaccine design and implementation in South America.


title: Work-related critical incidents in hospital-based health care providers and the risk of post-traumatic stress symptoms, anxiety, and depression: A meta-analysis

text: Abstract This meta-analysis reviewed existing data on the impact of work-related critical incidents in hospital-based health care professionals. Work-related critical incidents may induce post-traumatic stress symptoms or even post-traumatic stress disorder (PTSD), anxiety, and depression and may negatively affect health care practitioners’ behaviors toward patients. Nurses and doctors often cope by working part time or switching jobs. Hospital administrators and health care practitioners themselves may underestimate the effects of work-related critical incidents. Relevant online databases were searched for original research published from inception to 2009 and manual searches of the Journal of Traumatic Stress, reference lists, and the European Traumatic Stress Research Database were conducted. Two researchers independently decided on inclusion and study quality. Effect sizes were estimated using standardized mean differences with 95% confidence intervals. Consistency was evaluated, using the I 2-statistic. Meta-analysis was performed using the random effects model. Eleven studies, which included 3866 participants, evaluated the relationship between work-related critical incidents and post-traumatic stress symptoms. Six of these studies, which included 1695 participants, also reported on the relationship between work-related critical incidents and symptoms of anxiety and depression. Heterogeneity among studies was high and could not be accounted for by study quality, character of the incident, or timing of data collection. Pooled effect sizes for the impact of work-related critical incidents on post-traumatic stress symptoms, anxiety, and depression were small to medium. Remarkably, the effect was more pronounced in the longer than in the shorter term. In conclusion, this meta-analysis supports the hypothesis that work-related critical incidents are positively related to post-traumatic stress symptoms, anxiety, and depression in hospital-based health care professionals. Health care workers and their supervisors should be aware of the harmful effects of critical incidents and take preventive measures.


title: Chloroquine kills hair cells in zebrafish lateral line and murine cochlear cultures: Implications for ototoxicity

text: Hearing and balance deficits have been reported during and following treatment with the antimalarial drug chloroquine. However, experimental work examining the direct actions of chloroquine on mechanoreceptive hair cells in common experimental models is lacking. This study examines the effects of chloroquine on hair cells using two common experimental models: the zebrafish lateral line and neonatal mouse cochlear cultures. Zebrafish larvae were exposed to varying concentrations of chloroquine phosphate or hydroxychloroquine for 1 h or 24 h, and hair cells assessed by antibody staining. A significant, dose-dependent reduction in the number of surviving hair cells was seen across conditions for both exposure periods. Hydroxychloroquine showed similar toxicity. In mouse cochlear cultures, chloroquine damage was specific to outer hair cells in tissue from the cochlear basal turn, consistent with susceptibility to other ototoxic agents. These findings suggest a need for future studies employing hearing and balance monitoring during exposure to chloroquine and related compounds, particularly with interest in these compounds as therapeutics against viral infections including coronavirus.


title: Structural biology of the writers, readers, and erasers in mono- and poly(ADP-ribose) mediated signaling

text: ADP-ribosylation of proteins regulates protein activities in various processes including transcription control, chromatin organization, organelle assembly, protein degradation, and DNA repair. Modulating the proteins involved in the metabolism of ADP-ribosylation can have therapeutic benefits in various disease states. Protein crystal structures can help understand the biological functions, facilitate detailed analysis of single residues, as well as provide a basis for development of small molecule effectors. Here we review recent advances in our understanding of the structural biology of the writers, readers, and erasers of ADP-ribosylation.


title: Glucose 6 Phosphate Dehydrogenase Deficiency: An Actionable Risk Factor for Patients with COVID-19?

text: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked mutation that is more prevalent in African, Asian, Latin American and Mediterranean populations. Although most individuals are asymptomatic, exposure to certain food, drugs, or infections can trigger acute hemolytic anemia. Given the potential for coronavirus to trigger oxidative stress, unrecognized G6PD deficiency in the presence of the COVID-19 viral infection may cause hemolytic crisis and worse outcome in affected individuals. Further, since certain drugs that may be used to treat COVID-19 infection may cause hemolytic crisis in individuals with G6PD deficiency, it may be warranted to recommend adding G6PD deficiency to the list of screening elements in a COVID-19 workup for those patients where there is a high suspicion for this genetic mutation.


title: Improved antibiotic-free plasmid vector design by incorporation of transient expression enhancers

text: Methods to improve plasmid-mediated transgene expression are needed for gene medicine and gene vaccination applications. To maintain a low risk of insertional mutagenesis-mediated gene activation, expression-augmenting sequences would ideally function to improve transgene expression from transiently transfected intact plasmid, but not from spurious genomically integrated vectors. We report herein the development of potent minimal, antibiotic-free, high-manufacturing-yield mammalian expression vectors incorporating rationally designed additive combinations of expression enhancers. The SV40 72 bp enhancer incorporated upstream of the cytomegalovirus (CMV) enhancer selectively improved extrachromosomal transgene expression. The human T-lymphotropic virus type I (HTLV-I) R region, incorporated downstream of the CMV promoter, dramatically increased mRNA translation efficiency, but not overall mRNA levels, after transient transfection. A similar mRNA translation efficiency increase was observed with plasmid vectors incorporating and expressing the protein kinase R-inhibiting adenoviral viral associated (VA)1 RNA. Strikingly, HTLV-I R and VA1 did not increase transgene expression or mRNA translation efficiency from plasmid DNA after genomic integration. The vector platform, when combined with electroporation delivery, further increased transgene expression and improved HIV-1 gp120 DNA vaccine-induced neutralizing antibody titers in rabbits. These antibiotic-free vectors incorporating transient expression enhancers are safer, more potent alternatives to improve transgene expression for DNA therapy or vaccination. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/gt.2010.149) contains supplementary material, which is available to authorized users.


title: Bovine noroviruses: A missing component of calf diarrhoea diagnosis

text: Abstract Noroviruses are RNA viruses that belong to the Genus Norovirus, Family Caliciviridae, and infect human beings and several animal species, including cattle. Bovine norovirus infections have been detected in cattle of a range of different ages throughout the world. Currently there is no suitable cell culture system for these viruses and information on their pathogenesis is limited. Molecular and serological tests have been developed, but are complicated by the high genetic and antigenic diversity of bovine noroviruses. Bovine noroviruses can be detected frequently in faecal samples of diarrhoeic calves, either alone or in association with other common enteric pathogens, suggesting a role for these viruses in the aetiology of calf enteritis.


title: Vaccinology in the third millennium: scientific and social challenges

text: The epidemiology of deaths due to vaccine-preventable diseases has been significantly and positively altered through the use of vaccines. Despite this, significant challenges remain in vaccine development and use in the third millennium. Both new (Ebola, Chikungunya, West Nile) and re-emerging diseases (measles, mumps, influenza) require the development of new or next-generation vaccines. The global aging of the population, and accumulating numbers of immunocompromised persons, will require new vaccine and adjuvant development to protect large segments of the population. After vaccine development, significant challenges remain globally in the cost and efficient use and acceptance of vaccines by the public. This article raises issues in these two areas and suggests a way forward that will benefit current and future generations.


title: Kinetic characterization of trans-proteolytic activity of Chikungunya virus capsid protease and development of a FRET-based HTS assay

text: Chikungunya virus (CHIKV) capsid protein (CVCP) is a serine protease that possesses cis-proteolytic activity essential for the structural polyprotein processing and plays a key role in the virus life cycle. CHIKV being an emerging arthropod-borne pathogenic virus, is a public health concern worldwide. No vaccines or specific antiviral treatment is currently available for chikungunya disease. Thus, it is important to develop inhibitors against CHIKV enzymes to block key steps in viral reproduction. In view of this, CVCP was produced recombinantly and purified to homogeneity. A fluorescence resonance energy transfer (FRET)-based proteolytic assay was developed for high throughput screening (HTS). A FRET peptide substrate (DABCYL-GAEEWSLAIE-EDANS) derived from the cleavage site present in the structural polyprotein of CVCP was used. The assay with a Z’ factor of 0.64 and coefficient of variation (CV) is 8.68% can be adapted to high throughput format for automated screening of chemical libraries to identify CVCP specific protease inhibitors. Kinetic parameters K(m) and k(cat)/K(m) estimated using FRET assay were 1.26 ± 0.34 μM and 1.11 × 10(3) M(−1) sec(−1) respectively. The availability of active recombinant CVCP and cost effective fluorogenic peptide based in vitro FRET assay may serve as the basis for therapeutics development against CHIKV.


title: Cointegration between oil spot and future prices of the same and different grades in the presence of structural change

text: Abstract The purpose of this study is to examine whether crude oil spot and futures prices of the same and different grades are cointegrated using a residual-based cointegration test that allows for one structural break in the cointegrating vector and high-frequency data. We choose the US WTI and the UK Brent as the representative crudes for this analysis since these two crudes have well-established spot and futures markets. We find that spot and future prices of the same grade as well as spot and futures prices of different grades are cointegrated. We examine potential causes of structural change as revealed by the cointegration test in terms of events that have impacted on world oil markets as well as discuss the implications of the results for hedge managers, investors and regulators.


title: Eupatorium fortunei and Its Components Increase Antiviral Immune Responses against RNA Viruses

text: Eupatorium fortunei (EF) has long been used as herbal medicine in Korea, China, and Asian countries to treat a variety of diseases. Recent studies have reported that EF has anti-metastatic, anti-angiogenic, anti-bacterial, and anti-oxidant activities, as well as activities against malignant metastatic human cancers. The effect of EF and its components on viruses has not been reported. In the present study, the antiviral activity and mechanism of action of an aqueous extract of EF (WEF) and its components were evaluated in vitro. We found that pretreatment with WEF markedly reduced viral replication, as evaluated using a green fluorescent protein (GFP)-tagged virus (influenza A virus, Newcastle disease virus, and vesicular stomatitis virus) in murine RAW 264.7 macrophage cells. We demonstrated that WEF induces the production of type I IFN including pro-inflammatory cytokines. Additionally, we identified the active anti-viral components of WEF as quercetin, psoralen, and quercitrin. Thus, WEF and its active components are immunomodulators of the innate immune response in murine macrophages, a finding that is potentially useful to developing prophylactic or therapeutic treatments against a range of viruses.


title: Acute Rhinosinusitis in Children

text: Acute rhinosinusitis in children is a common disorder that is characterized by some or all of the following symptoms: fever, rhinorrhea, nasal congestion, cough, postnasal drainage, and facial pain/headache. It often starts as an upper respiratory tract infection that is complicated by a bacterial infection in which the symptoms worsen, persist, or are particularly severe. The accurate diagnosis of acute rhinosinusitis is challenging because of the overlap of symptoms with other common diseases, heavy reliance on subjective reporting of symptoms by the parents, and difficulties related to the physical examination of the child. Antibiotics are the mainstay of treatment. There is no strong evidence for the use of ancillary therapy. Orbital and intracranial complications may occur and are best treated early and aggressively. This article reviews the diagnosis, pathophysiology, bacteriology, treatment, and complications of acute rhinosinusitis in children.


title: Evolutionary history and stress regulation of the lectin superfamily in higher plants

text: BACKGROUND: Lectins are a class of carbohydrate-binding proteins. They play roles in various biological processes. However, little is known about their evolutionary history and their functions in plant stress regulation. The availability of full genome sequences from various plant species makes it possible to perform a whole-genome exploration for further understanding their biological functions. RESULTS: Higher plant genomes encode large numbers of lectin proteins. Based on their domain structures and phylogenetic analyses, a new classification system has been proposed. In this system, 12 different families have been classified and four of them consist of recently identified plant lectin members. Further analyses show that some of lectin families exhibit species-specific expansion and rapid birth-and-death evolution. Tandem and segmental duplications have been regarded as the major mechanisms to drive lectin expansion although retrogenes also significantly contributed to the birth of new lectin genes in soybean and rice. Evidence shows that lectin genes have been involved in biotic/abiotic stress regulations and tandem/segmental duplications may be regarded as drivers for plants to adapt various environmental stresses through duplication followed by expression divergence. Each member of this gene superfamily may play specialized roles in a specific stress condition and function as a regulator of various environmental factors such as cold, drought and high salinity as well as biotic stresses. CONCLUSIONS: Our studies provide a new outline of the plant lectin gene superfamily and advance the understanding of plant lectin genes in lineage-specific expansion and their functions in biotic/abiotic stress-related developmental processes.


title: Validation of the Arabic Version of the Early Childhood Oral Health Impact Scale (ECOHIS)

text: BACKGROUND: Assessment of the adverse effects of oral health problems on oral health-related quality of life (OHRQoL) is essential to ensure the well-being of children. The Early Childhood Oral Health Impact Scale (ECOHIS) is an instrument that was designed to assess caregivers’ perceptions of OHRQoL in preschool children. Although it has been translated into many languages, it has yet to be validated in Arabic. Therefore, this study aimed to translate this questionnaire to Arabic (A-ECOHIS) and test its psychometric properties. METHODS: Questionnaire responses from three samples of caregivers of preschool children ≤ 6 years of age were collected: (i) community-based (n = 422), from preschools selected as a stratified random sample; (ii) clinic-based, from those seeking pediatric dental care at a university clinic (n = 246); and (iii) a test-retest sample (n = 68), a clinic-based group of caregivers who completed questionnaires twice about siblings who were not receiving dental care. Children received a dental examination to assess their decayed, missed, filled teeth (dmft) scores. Convergent validity was evaluated by assessing the A-ECOHIS scores in relation to the response to a global question. Discriminant validity was evaluated by comparing the scores of children with varying levels of oral disease. Internal consistency was assessed by calculating Cronbach’s alpha, and the test-retest reliability was assessed using intra-class correlation coefficients (ICCs). RESULTS: The A-ECOHIS scores of the questionnaire sections and the global oral health rating were significantly correlated; Spearman correlation coefficients were, r = 0.55, P ≤ 0.01 (overall score), r = 0.54, P ≤ 0.01 (child section), and r = 0.51, P ≤ 0.01 (family section). The mean A-ECOHIS scores were also statistically significantly higher in children with higher dmft scores compared with lower dmft, and in the clinic-based sample compared with the community sample. The Cronbach’s alpha value of the the child, family sections and overall questionnaire were, 0.80, 0.78, and 0.85, respectively. The intra-class correlation coefficient (ICC) of A-ECOHIS was 0.86. CONCLUSION: The A-ECOHIS performed well on all psychometric tests to which it was applied. Thus, it is a valid and reliable instrument that can be used in Arabic-speaking caregivers of preschoolers aged 2 to 6 years.


title: Role of macrophages, interferon gamma and procoagulant activity in the resistance of genetic heterogeneous mouse populations to mouse hepatitis virus infection

text: Genetic heterogeneous mouse populations selected for high (H(III)) and low (L(III)) antibody response were used to study some aspects of mouse hepatitis virus 3 (MHV3) infection, such as the resistance pattern, virus replication in the liver and peritoneal exudate or in cultured peritoneal macrophages, the interferon (IFN) synthesis in the serum and peritoneal exudate and the procoagulant activity (PCA) of the peritoneal exudate (PEC) and spleen cells (SC). The H(III) mice, when compared to their L(III) mice counterparts, were susceptible to MHV3 infection showing higher virus titres in the liver and peritoneal exudate, comparable IFN alpha/beta or IFN gamma titres in the peritoneal exudate or in the serum, and higher levels of PCA of PEC and SC. A higher virus titre was detected in the supernatants of H(III) mouse macrophages infected with MHV3. The activation of H(III) mouse macrophages with LPS, IFN alpha/beta or IFN gamma, in contrast to that of L(III) mouse macrophages, did not induce an antiviral effect with partial restriction of the MHV3 replication. The LPS antiviral activity was shown to be partially exerted by IFN alpha/beta synthesis. The IFN gamma was shown to be more effective in inducing an antiviral state in L(III) macrophages, when compared to IFN alpha/beta. The data obtained are consistent with the notion that the resistance mechanisms to the MHV3 infection involve the PCA and the sensitivity of macrophages to IFN.


title: Characteristics of the Life Cycle of Porcine Deltacoronavirus (PDCoV) In Vitro: Replication Kinetics, Cellular Ultrastructure and Virion Morphology, and Evidence of Inducing Autophagy

text: Porcine deltacoronavirus (PDCoV) causes severe diarrhea and vomiting in affected piglets. The aim of this study was to establish the basic, in vitro characteristics of the life cycle such as replication kinetics, cellular ultrastructure, virion morphology, and induction of autophagy of PDCoV. Time-course analysis of viral subgenomic and genomic RNA loads and infectious titers indicated that one replication cycle of PDCoV takes 5 to 6 h. Electron microscopy showed that PDCoV infection induced the membrane rearrangements with double-membrane vesicles and large virion-containing vacuoles. The convoluted membranes structures described in alpha- and beta-coronavirus were not observed. PDCoV infection also increased the number of autophagosome-like vesicles in the cytoplasm of cells, and the autophagy response was detected by LC3 I/II and p62 Western blot analysis. For the first time, this study presents the picture of the PDCoV infection cycle, which is crucial to help elucidate the molecular mechanism of deltacoronavirus replication.


Mechanisms of Stroke in Coronavirus Disease 2019.


title: Evaluation of organ function in patients with severe COVID-19 infections

text: Abstract Objective: The purpose of our study was to assess organ function in 102 patients with severe COVID-19 infections, using retrospective clinical analysis. Material and Methods: A retrospective analysis was conducted on 102 patients with severe COVID-19 infections. The patients were divided into a survival group (n=73) and a non-survival group (n=29) according to their prognosis. The age, sex, underlying diseases, clinical laboratory data within 48 hours (routine blood tests, ALT, AST, TBIL, ALB, BUN, CR, D-Dimer, PT, APTT, FIB, F VIII:C, CK-MB, CK, and LDH), and ventilation status were collected. The organ functions of these severe COVID-19 patients were assessed by comparing the differences between the two groups. Results: AST, BUN, CR, CK-MB, LDH, and CK in the non-survival group were higher than those in the survival group, and the differences were statistically significant (P＜0.05). D-Dimer, PT, FIB, and F VIII:C in the non-survival group were higher than the values observed in the survival group, and the differences were statistically significant (P＜0.05). PLT, AST, BUN, CR, D-Dimer, PT, FIB, F VIII:C, CK-MB, CK, and LDH predicted the area under the ROC curve (AUC) of the COVID19 endpoint events and were 0.721, 0.854, 0.867, 0.757, 0.699, 0.679, 0.715, 0.811, 0.935, and 0.802, respectively. Conclusion: The results showed that there were different degrees of damage to the liver, kidneys, blood coagulation, and heart function in the non-survival group. In addition, PLT, AST, BUN, CR, D-Dimer, PT, FIB, F VIII:C, CK-MB, CK, and LDH had value in evaluating disease prognosis.