title: Infants with Atypical Presentations of Alveolar Capillary Dysplasia with Misalignment of the Pulmonary Veins Who Underwent Bilateral Lung Transplantation

text: Objective To describe disease course, histopathology, and outcomes for infants with atypical presentations of alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) who underwent bilateral lung transplantation. Study design We reviewed clinical history, diagnostic studies, explant histology, genetic sequence results, and post-transplant course for 6 infants with atypical ACDMPV who underwent bilateral lung transplantation at St. Louis Children's Hospital. We compared their histology with infants with classic ACDMPV and compared their outcomes with infants transplanted for other indications. Results In contrast with neonates with classic ACDPMV who present with severe hypoxemia and refractory pulmonary hypertension within hours of birth, none of the infants with atypical ACDMPV presented with progressive neonatal respiratory failure. Three infants had mild neonatal respiratory distress and received nasal cannula oxygen. Three other infants had no respiratory symptoms at birth and presented with hypoxemia and pulmonary hypertension at 2-3 months of age. Bilateral lung transplantation was performed at 4-20 months of age. Unlike in classic ACDMPV, histopathologic findings were not distributed uniformly and were not diffuse. Three subjects had apparent nonmosaic genetic defects involving FOXF1. Two infants had extrapulmonary anomalies (posterior urethral valves, inguinal hernia). Three transplanted children are alive at 5-16 years of age, similar to outcomes for infants transplanted for other indications. Lung explants from infants with atypical ACDMPV demonstrated diagnostic but nonuniform histopathologic findings. Conclusions The 1- and 5-year survival rates for infants with atypical ACDMPV are similar to infants transplanted for other indications. Given the clinical and histopathologic spectra, ACDMPV should be considered in infants with hypoxemia and pulmonary hypertension, even beyond the newborn period.


title: Suggested management of immunocompromized kidney patients suffering from SARS

text: The treatment of severe acute respiratory syndrome (SARS) is still empirical and controversial. Herein we report our experience in treating approximately 40 SARS children and adolescents. Treatment of SARS kidney patients is limited. Paediatric nephrologists should be on the alert for SARS in order to care for immunocompromised patients. Precautions should be made for both staff and patients with protective measures for infection control.


title: Transmission cycles, host range, evolution and emergence of arboviral disease

text: Many pandemics have been attributed to the ability of some RNA viruses to change their host range to include humans. Here, we review the mechanisms of disease emergence that are related to the host-range specificity of selected mosquito-borne alphaviruses and flaviviruses. We discuss viruses of medical importance, including Venezuelan equine and Japanese encephalitis viruses, dengue viruses and West Nile viruses.


title: Follow up of aerobic capacity in children affected by severe acute respiratory syndrome

text: Background and objective: The aim of this study was to investigate the aerobic capacity of children 3 years after they were diagnosed with severe acute respiratory syndrome (SARS). Methods: Twenty‐seven patients who completed both pulmonary function and maximal aerobic capacity tests at 6 and 15 months after the acute illness were invited to return for reassessment. Results: Twenty‐one patients (median age 18.2 years, interquartile range (IQR) 16.5–19.7) completed all investigations at 36 months. Pulmonary function was normal in all patients. Maximal aerobic capacity, peak oxygen pulse (peak VO(2)) and ventilatory anaerobic threshold showed significant improvements compared with values measured at 6 months in both boys and girls. In girls, ventilatory efficiency (ventilatory equivalents for oxygen and carbon dioxide) and perfusion of the lungs (end‐tidal partial carbon dioxide pressure) had not increased further compared with the values measured at 15 months. Although peak VO(2) improved further at 36 months in patients with or without persistent radiological abnormalities, the values were 68% (IQR 50–84) and 74% (IQR 60–99), respectively, of those for normal control subjects. Conclusions: There were improvements in aerobic capacity at 36 months in children affected by SARS; however, the measured values remained suboptimal.


Less is more: Intelligent intensive care for SARS-CoV-2 based on the imaging data


Clinical Research and Trials—A “Nonessential” Victim of the COVID-19 Pandemic?


title: Effect of COVID‐19 on liver transplantation in Korea

text: COVID‐19 is now a pandemic with increasing numbers of cases and deaths. In addition to the economic and social damage caused by COVID‐19 outbreak prolongation, damage caused by delayed treatment of other diseases such as severe cirrhosis is also serious. We aimed to describe the effect of COVID‐19 on the number of liver transplants (LT) in South Korea. The number of LT performed in Korea during the Middle East Respiratory Syndrome (MERS) outbreak, and the COVID‐19 pandemic was compared with the average number of LT performed in the past 5 years. There were 108.5 cases of LT performed per month during the MERS outbreak. It was 11% lower than the average of 122.8 cases per month for the last 5 years. LDLT and DDLT decreased by 13% to 75.3 cases and by 7.5% to 33.2 cases per month during the MERS epidemic, respectively. From January to March 2020 (COVID‐19 outbreak), the number of LT did not decrease significantly. The lockdown caused by COVID‐19 did not affect the number of liver transplants in Korea. Establishing a safe process and procedure of liver transplantation within safe boundaries can be beneficial in reducing the side effects of lockdown and saving patients' lives.


title: The United States and Canada as a coupled epidemiological system: An example from hepatitis A

text: BACKGROUND: Hepatitis A (HA) is a low-incidence, non-endemic disease in Canada and the United States (US). However, a large difference in HA incidence between Canada and HA-endemic countries has made travel an important contributor to hepatitis A prevalence in Canada. There is also a (smaller) incidence differential between Canada and the US. Although the US has only moderately higher HA incidence, the volume of travel by Canadians to the US is many times higher than travel volume to endemic countries. Hence, travel to the US may constitute a source of low to moderate risk for Canadian travelers. To our knowledge, travel to the US has never been included as a potential risk factor for HA infection in Canadian epidemiologic analyses. The objective of this study was to use dynamic models to investigate the possible effects on hepatitis A incidence in Canada due to (1) implementing vaccination in the US, and (2) varying the volume of travel by Canadians to the US. METHODS: We developed and analyzed age-structured compartmental models for the transmission and vaccination of hepatitis A, for both Canada and the US. Models were parameterized using data on seroprevalence, case reporting, and travel patterns. The potential effect of hepatitis A prevalence in the US on hepatitis A prevalence in Canada was captured through a term representing infection of Canadians due to travel in the US. RESULTS: The model suggests that approximately 22% of HA cases in Canada in the mid 1990s may have been attributable to travel to the US. A universal vaccination programme that attained 70% coverage in young children in the US in the mid 1990s could have reduced Canadian incidence by 21% within 5 years. CONCLUSION: Since not all necessary data were available to parameterize the model, the results should be considered exploratory. However, the analysis shows that, under plausible assumptions, the US may be more important for determining HA prevalence in Canada than is currently supposed. As international travel continues to grow, making vaccination policies ever more relevant to populations beyond a country's borders, such multi-country models will most likely come into wider use as predictive aids for policy development.


title: Complete Genome Sequence of Middle East Respiratory Syndrome Coronavirus Isolated from a Dromedary Camel in Egypt

text: We generated the near-full genome sequence of Middle East respiratory syndrome coronavirus (MERS-CoV) from a collected nasal sample of dromedary camel in Egypt. The newly characterized Egyptian strain has high similarity to the previously characterized Egyptian virus and both of viruses fell into a cluster distinct from other MERS-CoVs.


title: Can rewiring strategy control the epidemic spreading?

text: Abstract Relation existed in the social contact network can affect individuals’ behaviors greatly. Considering the diversity of relation intimacy among network nodes, an epidemic propagation model is proposed by incorporating the link-breaking threshold, which is normally neglected in the rewiring strategy. The impact of rewiring strategy on the epidemic spreading in the weighted adaptive network is explored. The results show that the rewiring strategy cannot always control the epidemic prevalence, especially when the link-breaking threshold is low. Meanwhile, as well as strong links, weak links also play a significant role on epidemic spreading.


title: Complete Genome Sequence of Human Coronavirus OC43 Isolated from Mexico

text: We report the complete genome sequence of the first Mexican human coronavirus (HCoV) OC43, obtained by new-generation sequencing and a metagenomic approach, isolated from a child hospitalized with pneumonia. The genome is closely related to the other OC43 genome sequences available, ranging from 99.8% to 98.2% nucleotide sequence identity.


title: Molecular diagnosis of viral diseases, present trends and future aspects: A view from the OIE Collaborating Centre for the Application of Polymerase Chain Reaction Methods for Diagnosis of Viral Diseases in Veterinary Medicine

text: The emergence and re-emergence of transboundary animal diseases (TADs), e.g., foot-and-mouth disease, classical swine fever and the highly pathogenic avian influenza strongly indicate the need for the development of powerful and robust new diagnostic methods. The experiences of an OIE-Collaborating Centre and of two EU project consortia are summarised on the diagnostic application of gel-based PCR, general PCR systems, phylogeny, molecular epidemiology, real-time PCR (TaqMan, Molecular Beacons, Primer-Probe Energy Transfer), amplification without thermocycling (Invader), multiplex PCR, nucleic acid extraction and pipetting robotics, automation and quality control, including internal controls. By following the steps of OIE validation, the diagnostic assays are nationally and internationally standardised. The development of padlock probes and microarrays, as well as ultra rapid PCR and sequencing methods is further improving the arsenal of nucleic acid based molecular diagnosis. Further trends of diagnostic development are also mentioned, in order to combat TADs and other viral infections more effectively in the future.


The evolving role of the renin–angiotensin system in ARDS


title: Perspectives of Cancer Patients and Their Health during the COVID-19 Pandemic

text: Introduction The immunosuppressive nature of some cancers and many cancer-directed treatments may increase the risk of infection with and severe sequelae from Coronavirus Disease 2019 (COVID-19). The objective of this study was to compare concerns about COVID-19 among individuals undergoing cancer treatment to those with a history of cancer not currently receiving therapy and to those without a cancer history. Methods We conducted a cross-sectional anonymous online survey study of adults currently residing in the United States. Participants were recruited over a one-week period (April 3-11, 2020) using promoted advertisements on Facebook and Twitter. Groups were compared using chi-squared tests, Fisher's exact tests, and t-tests. Results 543 respondents from 47 states provided information on their cancer history and were included in analyses. Participants receiving active treatment reported greater concern about coronavirus infection (p<0.0001), higher levels of family distress caused by the COVID-19 pandemic (p=0.004), and greater concern that the general public does not adequately understand the seriousness of COVID-19 (p=0.04). Those with metastatic disease were more likely to indicate that COVID-19 had negatively affected their cancer care compared to patients with non-metastatic cancer (50.8% vs. 31.0%; p=0.02). The most commonly reported treatment modifications included chemotherapy delays. Conclusions Patients undergoing active treatment for cancer were most concerned about the short-term effects of the COVID-19 pandemic on the logistics as well as potential efficacy of ongoing cancer treatment, longer term effects, and overarching societal concerns that the population at large is not as concerned about the public health implications of the coronavirus.


title: PCR Improves Diagnostic Yield from Lung Aspiration in Malawian Children with Radiologically Confirmed Pneumonia

text: BACKGROUND: Accurate data on childhood pneumonia aetiology are essential especially from regions where mortality is high, in order to inform case-management guidelines and the potential of prevention strategies such as bacterial conjugate vaccines. Yield from blood culture is low, but lung aspirate culture provides a higher diagnostic yield. We aimed to determine if diagnostic yield could be increased further by polymerase chain reaction (PCR) detection of bacteria (Streptococcus pneumoniae and Haemophilus influenzae b) and viruses in lung aspirate fluid. METHODS: A total of 95 children with radiological focal, lobar or segmental consolidation had lung aspirate performed and sent for bacterial culture and for PCR for detection of bacteria, viruses and Pneumocystis jirovecii. In children with a pneumococcal aetiology, pneumococcal bacterial loads were calculated in blood and lung aspirate fluid. RESULTS: Blood culture identified a bacterial pathogen in only 8 patients (8%). With the addition of PCR on lung aspirate samples, causative pathogens (bacterial, viral, pneumocystis) were identified singly or as co-infections in 59 children (62%). The commonest bacterial organism was S.pneumoniae (41%), followed by H. influenzae b (6%), and the commonest virus identified was adenovirus (16%), followed by human bocavirus (HBoV) (4%), either as single or co-infection. CONCLUSIONS: In a select group of African children, lung aspirate PCR significantly improves diagnostic yield. Our study confirms a major role of S.pneumoniae and viruses in the aetiology of childhood pneumonia in Africa.


title: Are there any differences in clinical and laboratory findings on admission between H1N1 positive and negative patients with flu-like symptoms?

text: BACKGROUND: The World Health Organization alert for the H1N1 influenza pandemic led to the implementation of certain measures regarding admission of patients with flu-like symptoms. All these instructions were adopted by the Greek National Health System. The aim of this study was to retrospectively examine the characteristics of all subjects admitted to the Unit of Infectious Diseases with symptoms indicating H1N1 infection, and to identify any differences between H1N1 positive or negative patients. Patients from the ED (emergency department) with flu-like symptoms (sore throat, cough, rhinorhea, or nasal congestion) and fever >37.5°C were admitted in the Unit of Infectious diseases and gave pharyngeal or nasopharyngeal swabs. Swabs were tested with real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR). FINDINGS: Patients were divided into two groups. Group A comprised 33 H1N1 positive patients and Group B (control group) comprised of 27 H1N1 negative patients. The two groups did not differ in terms of patient age, co-morbidities, length of hospitalization, temperature elevation, hypoxemia, as well as renal and liver function. There were also no significant differences in severity on admission. C-reactive protein (CRP) (mean 12.8 vs. 5.74) and white blood count (WBC) (mean 10.528 vs. 7.114) were significantly higher in group B than in group A upon admission. Obesity was noted in 8 patients of Group A (mean 31.67) and 14 patients of Group B (mean 37.78). Body mass index (BMI) was lower in H1N1 positive than in H1N1 negative patients (mean 31.67 vs. 37.78, respectively; p = 0.009). CONCLUSIONS: The majority of patients in both groups were young male adults. CRP, WBC and BMI were higher among H1N1 negative patients. Finally, clinical course of patients in both groups was mild and uneventful.


title: AntiVPP 1.0: A portable tool for prediction of antiviral peptides

text: Abstract Viruses are worldwide pathogens with a high impact on the human population. Despite the constant efforts to fight viral infections, there is a need to discover and design new drug candidates. Antiviral peptides are molecules with confirmed activity and constitute excellent alternatives for the treatment of viral infections. In the present study, we developed AntiVPP 1.0, an accurate bioinformatic tool that uses the Random Forest algorithm for antiviral peptide predictions. The model of AntiVPP 1.0 for antiviral peptide predictions uses several features of 1088 peptides for training and validation. During the validation of the model we achieved the TPR = 0.87, SPC = 0.97, ACC = 0.93 and MCC = 0.87 performance measures, which were indicative of a robust model. AntiVPP 1.0 is a fast, accurate and intuitive software focused on the assessment of antiviral peptides candidates. AntiVPP 1.0 is available at https://github.com/bio-coding/AntiVPP.


title: Evolutionary Insights into IL17A in Lagomorphs

text: In leporids, IL17A had been implicated in the host defense against extracellular pathogens, such as Francisella tularensis that infects hares and rabbits and causes the zoonotic disease tularemia. Here, we studied IL17A from five lagomorphs, European rabbit, pygmy rabbit, brush rabbit, European brown hare, and American pika. We observed that this protein is highly conserved between these species, with a similarity of 97–99% in leporids and ~88% between leporids and American pika. The exon/intron structure, N-glycosylation sites, and cysteine residues are conserved between lagomorphs. However, at codon 88, one of the interaction sites between IL17A and its receptor IL17RA, there is an Arg>Pro mutation that only occurs in European rabbit and European brown hare. This could induce critical alterations in the IL17A structure and conformation and consequently modify its function. The differences observed between leporids and humans or rodents might also represent important alterations in protein structure and function. In addition, as for other interleukins, IL17A sequences of human and European rabbit are more closely related than the sequences of human and mouse or European rabbit and mouse. This study gives further support to the hypothesis that European rabbit might be a more suitable animal model for studies on human IL17.


title: Compliance and Psychological Impact of Quarantine in Children and Adolescents due to Covid-19 Pandemic

text: OBJECTIVES: To examine a cohort of children and adolescents quarantined during Coronavirus disease 2019 outbreak in India and to describe their understanding of, compliance with and the psychological impact of quarantine experience. METHODS: One hundred twenty one children and adolescents along with their parents were interviewed regarding their compliance and psychological distress during the quarantine period. A comparable data was also obtained from 131 children and adolescents who were not quarantined. RESULTS: Most of the children and adolescents were non-compliant as compliance with all requirements was low (7.43%), though compliance with community protective measures (17.35%) was better than compliance with household protective measures (10.71%). Quarantined children and adolescents experienced greater psychological distress than non-quarantined children and adolescents (p ˂0.001). Worry (68.59%), helplessness (66.11%) and fear (61.98%) were the most common feelings experienced under quarantine. CONCLUSIONS: The low compliance with quarantine requirements as seen in this study raises a serious concern about the effectiveness of quarantine as a preventive measure of disease transmission. Compliance and mental health problems can be improved by providing adequate financial support and enhanced knowledge about pandemic planning.


Hydroxychloroquine and Azithromycin to Treat Patients With COVID‐19: Both Friends and Foes?


title: Mathematical modeling of the West Africa Ebola epidemic

text: As of November 2015, the Ebola virus disease (EVD) epidemic that began in West Africa in late 2013 is waning. The human toll includes more than 28,000 EVD cases and 11,000 deaths in Guinea, Liberia, and Sierra Leone, the most heavily-affected countries. We reviewed 66 mathematical modeling studies of the EVD epidemic published in the peer-reviewed literature to assess the key uncertainties models addressed, data used for modeling, public sharing of data and results, and model performance. Based on the review, we suggest steps to improve the use of modeling in future public health emergencies. DOI: http://dx.doi.org/10.7554/eLife.09186.001


title: Modelling the epidemic trend of the 2019 novel coronavirus outbreak in China

text: We present a timely evaluation of the Chinese 2019-nCov epidemic in its initial phase, where 2019-nCov demonstrates comparable transmissibility but lower fatality rates than SARS and MERS. A quick diagnosis that leads to case isolation and integrated interventions will have a major impact on its future trend. Nevertheless, as China is facing its Spring Festival travel rush and the epidemic has spread beyond its borders, further investigation on its potential spatiotemporal transmission pattern and novel intervention strategies are warranted.


title: Serological survey of Encephalitozoon cuniculi infection in cats in Japan

text: Antibodies to Encephalitozoon cuniculi (E. cuniculi) were examined by enzyme-linked immunosorbent assay using E. cuniculi PTP2 recombinant protein from serum samples that had been collected from a total of 295 cats in Japan. Of these samples, 6.1% (18/295) had antibodies against E. cuniculi, which included 6.3% (6/96) of the male cats and 6.0% (12/199) of the female cats. The incidence was slightly higher in feral cats (8.3%, 11/132) compared to domesticated cats (4.3%, 7/163). This suggests the possibility that the cats of our country have become a reservoir of E. cuniculi. This study is the first to demonstrate the prevalence of E. cuniculi infection in cats in Japan.


title: Estimation of SARS-CoV-2 infection fatality rate by real-time antibody screening of blood donors

text: BACKGROUND: The pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has tremendous consequences for our societies. Knowledge of the seroprevalence of SARS-CoV-2 is needed to accurately monitor the spread of the epidemic and to calculate the infection fatality rate (IFR). These measures may help the authorities to make informed decisions and adjust the current societal interventions. The objective was to perform nationwide real-time seroprevalence surveying among blood donors as a tool to estimate previous SARS-CoV-2 infections and the population based IFR. METHODS: Danish blood donors aged 17–69 years giving blood April 6 to May 3 were tested for SARS-CoV-2 immunoglobulin M and G antibodies using a commercial lateral flow test. Antibody status was compared between geographical areas and an estimate of the IFR was calculated. The seroprevalence was adjusted for assay sensitivity and specificity taking the uncertainties of the test validation into account when reporting the 95% confidence intervals (CI). RESULTS: The first 20,640 blood donors were tested and a combined adjusted seroprevalence of 1.9% (CI: 0.8-2.3) was calculated. The seroprevalence differed across areas. Using available data on fatalities and population numbers a combined IFR in patients younger than 70 is estimated at 89 per 100,000 (CI: 72-211) infections. CONCLUSIONS: The IFR was estimated to be slightly lower than previously reported from other countries not using seroprevalence data. The IFR is likely several fold lower than the current estimate. We have initiated real-time nationwide anti-SARS-CoV-2 seroprevalence surveying of blood donations as a tool in monitoring the epidemic.


title: Coronavirus-positive Nasopharyngeal Aspirate as Predictor for Severe Acute Respiratory Syndrome Mortality

text: Severe acute respiratory syndrome (SARS) has caused a major epidemic worldwide. A novel coronavirus is deemed to be the causative agent. Early diagnosis can be made with reverse transcriptase-polymerase chain reaction (RT-PCR) of nasopharyngeal aspirate samples. We compared symptoms of 156 SARS-positive and 62 SARS-negative patients in Hong Kong; SARS was confirmed by RT-PCR. The RT-PCR–positive patients had significantly more shortness of breath, a lower lymphocyte count, and a lower lactate dehydrogenase level; they were also more likely to have bilateral and multifocal chest radiograph involvement, to be admitted to intensive care, to need mechanical ventilation, and to have higher mortality rates. By multivariate analysis, positive RT-PCR on nasopharyngeal aspirate samples was an independent predictor of death within 30 days.


title: Detection of bat coronaviruses from Miniopterus fuliginosus in Japan

text: Bats have great potential as reservoirs for emerging viruses such as severe acute respiratory syndrome-coronavirus. In this study, bat coronaviruses (BtCoVs) were detected by RT-PCR from intestinal and fecal specimens of Miniopterus fuliginosus breeding colonies in Wakayama Prefecture caves, where we previously identified bat betaherpesvirus 2. Two primer sets were used for the detection of BtCoV: one was for the RNA-dependent RNA polymerase (RdRp) region and the other was for the spike (S) protein region. Eleven and 73% of intestinal and fecal specimens, respectively, were positive for RdRp region, and 2 and 40% of those were positive for S protein region. Sequencing and phylogenetic analysis showed that the detected BtCoV belonged to the group 1 (alpha) coronaviruses. These data suggest that BtCoV is endemic in M. fuliginosus in Japan.


Policies and procedures for personal protective equipment: does inconsistency increase risk of contamination and infection?


Oral and Nasal Decontamination for COVID-19 Patients: More Harm Than Good?


title: Recognition of aerosol transmission of infectious agents: a commentary

text: Although short-range large-droplet transmission is possible for most respiratory infectious agents, deciding on whether the same agent is also airborne has a potentially huge impact on the types (and costs) of infection control interventions that are required. The concept and definition of aerosols is also discussed, as is the concept of large droplet transmission, and airborne transmission which is meant by most authors to be synonymous with aerosol transmission, although some use the term to mean either large droplet or aerosol transmission. However, these terms are often used confusingly when discussing specific infection control interventions for individual pathogens that are accepted to be mostly transmitted by the airborne (aerosol) route (e.g. tuberculosis, measles and chickenpox). It is therefore important to clarify such terminology, where a particular intervention, like the type of personal protective equipment (PPE) to be used, is deemed adequate to intervene for this potential mode of transmission, i.e. at an N95 rather than surgical mask level requirement. With this in mind, this review considers the commonly used term of ‘aerosol transmission’ in the context of some infectious agents that are well-recognized to be transmissible via the airborne route. It also discusses other agents, like influenza virus, where the potential for airborne transmission is much more dependent on various host, viral and environmental factors, and where its potential for aerosol transmission may be underestimated.


title: Entrepreneurship in a Transformative and Resource-Rich State: The Case of Qatar

text: Abstract Countries blessed with natural resources have generally struggled to achieve sustainable economic development and prosperity. Population growth, the depletion of natural resources coupled with mismanagement, and sharp fluctuations in prices of those resources are among the main reasons for sub-optimal economic performance. Some resource-rich countries have been expending effort and money in an attempt to change this inverse relationship (a.k.a. “the resource curse”) by designing policies to diversify their economies with high value-added industries and sectors. Qatar is a such country and point of the interest in this article. Qatar's political and economic structure, its efforts to diversify its economy, and the potential for improved entrepreneurial outcomes with high value-added products, services, businesses, and industries are analyzed. The country has been very effective in maximizing the benefits of its oil resources and especially its large natural gas reserves, becoming the largest exporter of liquefied natural gas (LNG) in the world. Revenues from oil and gas sales have been invested in the domestic economy and global assets. Thus far, however, it has not shown the in-house capacity for innovation and entrepreneurship critical for sustainable economic diversification going forward. This publication was made possible in part by NPRP grant #10-1203-160007 from the Qatar National Research Fund (a member of the Qatar Foundation).


title: Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia

text: Pneumonia may be caused by a wide range of pathogens and is considered the most common infectious cause of death in humans. Murine acute lung infection models mirror human pathologies in many aspects and contribute to our understanding of the disease and the development of novel treatment strategies. Despite progress in other fields of tissue imaging, histopathology remains the most conclusive and practical read out tool for the descriptive and semiquantitative evaluation of mouse pneumonia and therapeutic interventions. Here, we systematically describe and compare the distinctive histopathological features of established models of acute pneumonia in mice induced by Streptococcus (S.) pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Legionella pneumophila, Escherichia coli, Middle East respiratory syndrome (MERS) coronavirus, influenza A virus (IAV) and superinfection of IAV-incuced pneumonia with S. pneumoniae. Systematic comparisons of the models revealed striking differences in the distribution of lesions, the characteristics of pneumonia induced, principal inflammatory cell types, lesions in adjacent tissues, and the detectability of the pathogens in histological sections. We therefore identified core criteria for each model suitable for practical semiquantitative scoring systems that take into account the pathogen- and model-specific patterns of pneumonia. Other critical factors that affect experimental pathologies are discussed, including infectious dose, time kinetics, and the genetic background of the mouse strain. The substantial differences between the model-specific pathologies underscore the necessity of pathogen- and model-adapted criteria for the comparative quantification of experimental outcomes. These criteria also allow for the standardized validation and comparison of treatment strategies in preclinical models.


title: Structure, stability and function of RNA pseudoknots involved in stimulating ribosomal frameshifting 1 1 Edited by D. E. Draper

text: Abstract Programmed −1 ribosomal frameshifting has become the subject of increasing interest over the last several years, due in part to the ubiquitous nature of this translational recoding mechanism in pathogenic animal and plant viruses. All cis-acting frameshift signals encoded in mRNAs are minimally composed of two functional elements: a heptanucleotide “slippery sequence” conforming to the general form X XXY YYZ, followed by an RNA structural element, usually an H-type RNA pseudoknot, positioned an optimal number of nucleotides (5 to 9) downstream. The slippery sequence itself promotes a low level (≈1 %) of frameshifting; however, downstream pseudoknots stimulate this process significantly, in some cases up to 30 to 50 %. Although the precise molecular mechanism of stimulation of frameshifting remains poorly understood, significant advances have been made in our knowledge of the three-dimensional structures, thermodynamics of folding, and functional determinants of stimulatory RNA pseudoknots derived from the study of several well-characterized frameshift signals. These studies are summarized here and provide new insights into the structural requirements and mechanism of programmed −1 ribosomal frameshifting.


title: Acute Respiratory Failure and Chronic Obstructive Lung Disease

text: Patients with COPD who develop acute respiratory failure require special attention in their management. Patients with severe COPD often have cor pulmonale, complex acid/base compensations, and altered respiratory control mechanisms. These need to be considered when approaching the patient with an acute decompensation. Because of the improving prognosis in this group of patients, aggressive management should be undertaken using combinations of bronchodilator medications, oxygen, bronchial hygiene, and antibiotics.


Callous attitude toward doctors during COVID‐19


title: Virus detections among patients with severe acute respiratory illness, Northern Vietnam

text: Severe acute respiratory illness (SARI) is a major cause of death and morbidity in low- and middle-income countries, however, the etiologic agents are often undetermined due to the lack of molecular diagnostics in hospitals and clinics. To examine evidence for select viral infections among patients with SARI in northern Vietnam, we studied 348 nasopharyngeal samples from military and civilian patients admitted to 4 hospitals in the greater Hanoi area from 2017–2019. Initial screening for human respiratory viral pathogens was performed in Hanoi, Vietnam at the National Institute of Hygiene and Epidemiology (NIHE) or the Military Institute of Preventative Medicine (MIPM), and an aliquot was shipped to Duke-NUS Medical School in Singapore for validation. Patient demographics were recorded and used to epidemiologically describe the infections. Among military and civilian cases of SARI, 184 (52.9%) tested positive for one or more respiratory viruses. Influenza A virus was the most prevalent virus detected (64.7%), followed by influenza B virus (29.3%), enterovirus (3.8%), adenovirus (1.1%), and coronavirus (1.1%). Risk factor analyses demonstrated an increased risk of influenza A virus detection among military hospital patients (adjusted OR, 2.0; 95% CI, 1.2–3.2), and an increased risk of influenza B virus detection among patients enrolled in year 2017 (adjusted OR, 7.9; 95% CI, 2.7–22.9). As influenza A and B viruses were commonly associated with SARI and are treatable, SARI patients entering these hospitals would benefit if the hospitals were able to adapt onsite molecular diagnostics.


title: Vaccinia Virus as a Master of Host Shutoff Induction: Targeting Processes of the Central Dogma and Beyond

text: The synthesis of host cell proteins is adversely inhibited in many virus infections, whereas viral proteins are efficiently synthesized. This phenomenon leads to the accumulation of viral proteins concurrently with a profound decline in global host protein synthesis, a phenomenon often termed “host shutoff”. To induce host shutoff, a virus may target various steps of gene expression, as well as pre- and post-gene expression processes. During infection, vaccinia virus (VACV), the prototype poxvirus, targets all major processes of the central dogma of genetics, as well as pre-transcription and post-translation steps to hinder host cell protein production. In this article, we review the strategies used by VACV to induce host shutoff in the context of strategies employed by other viruses. We elaborate on how VACV induces host shutoff by targeting host cell DNA synthesis, RNA production and processing, mRNA translation, and protein degradation. We emphasize the topics on VACV’s approaches toward modulating mRNA processing, stability, and translation during infection. Finally, we propose avenues for future investigations, which will facilitate our understanding of poxvirus biology, as well as fundamental cellular gene expression and regulation mechanisms.


title: The Impact of the Interferon/TNF-Related Apoptosis-Inducing Ligand Signaling Axis on Disease Progression in Respiratory Viral Infection and Beyond

text: Interferons (IFNs) are well described to be rapidly induced upon pathogen-associated pattern recognition. After binding to their respective IFN receptors and activation of the cellular JAK/signal transducer and activator of transcription signaling cascade, they stimulate the transcription of a plethora of IFN-stimulated genes (ISGs) in infected as well as bystander cells such as the non-infected epithelium and cells of the immune system. ISGs may directly act on the invading pathogen or can either positively or negatively regulate the innate and adaptive immune response. However, IFNs and ISGs do not only play a key role in the limitation of pathogen spread but have also been recently found to provoke an unbalanced, overshooting inflammatory response causing tissue injury and hampering repair processes. A prominent regulator of disease outcome, especially in—but not limited to—respiratory viral infection, is the IFN-dependent mediator TRAIL (TNF-related apoptosis-inducing ligand) produced by several cell types including immune cells such as macrophages or T cells. First described as an apoptosis-inducing agent in transformed cells, it is now also well established to rapidly evoke cellular stress pathways in epithelial cells, finally leading to caspase-dependent or -independent cell death. Hereby, pathogen spread is limited; however in some cases, also the surrounding tissue is severely harmed, thus augmenting disease severity. Interestingly, the lack of a strictly controlled and well balanced IFN/TRAIL signaling response has not only been implicated in viral infection but might furthermore be an important determinant of disease progression in bacterial superinfections and in chronic respiratory illness. Conclusively, the IFN/TRAIL signaling axis is subjected to a complex modulation and might be exploited for the evaluation of new therapeutic concepts aiming at attenuation of tissue injury.


title: Microbes, Helminths and Rheumatic Diseases

text: Abstract There has been a progressive interest on the modifications of the human defense system following insults occurring in the interface between our body and the external environment, as they may provoke or worsen disease states. Studies suggest the billions of germs that compose the gut microbiota influence one’s innate and adaptive immune responses at the intestinal level, but these microorganisms may also impact rheumatic diseases. The microbiota of the skin, respiratory and urinary tracts may also be relevant in rheumatology. Evidence indicates that changes in the gut microbiome alter the pathogenesis of immune-mediated diseases such as rheumatoid arthritis and ankylosing spondylitis but also of other disorders like atherosclerosis and osteoarthritis. Therapeutic strategies to modify the microbiota, including probiotics and fecal microbiota transplantation, have been received with skepticism, which, in turn, has drawn attention back to previously developed interventions such as antibiotics. Helminths adapted to humans over the evolution process, but their role in disease modulation, particularly immune-mediated diseases, remains to be understood. The present review focuses on data concerning modifications of the immune system induced by interactions with microbes and pluricellular organisms, namely helminths, and their impact on rheumatic diseases. Practical aspects, including specific microbiota-targeted therapies, are also discussed.


title: Physical activity in a pandemic: A new treatment target for psychological therapy

text: The COVID‐19 pandemic and its management are placing significant new strains on people’s well‐being, particularly those with pre‐existing mental health conditions. Physical activity has been shown to improve mental as well as physical health. Increasing activity levels should be prioritized as a treatment target, especially when the barriers to exercise are greater than ever. Promoting physical activity has not traditionally been the remit of psychologists. Yet psychological theory and therapeutic techniques can be readily applied to address physical inactivity. We present theoretical perspectives and therapy techniques relating to (1) beliefs about physical activity, (2) motivation to be physically active, and (3) the sense of reward achieved through being physically active. We outline strategies to initiate and maintain physical activity during the COVID‐19 pandemic, thereby benefitting mental and physical health. COVID‐19 is demanding rapid and substantial change across the whole health care system. Psychological therapists can respond creatively by addressing physical activity, a treatable clinical target which delivers both mental and physical health benefits. PRACTITIONER POINTS: Physical activity is essential for our mental and physical health. Yet COVID‐19 presents novel barriers to physical activity. Psychological theory and techniques to address beliefs, motivation, and reward can be applied to increase physical activity during COVID‐19. Physical activity is an important clinical target to sustain and improve mental health, especially in the current pandemic.


Adapting urology residency training in the COVID-19 era


UTILIDAD DE LA ECOGRAFÍA TORÁCICA EN INFECCIÓN NEONATAL POR SARS-CoV-2


title: A prospective case-control study on the association of Rhinovirus nasopharyngeal viral load and viremia in South African children hospitalized with severe pneumonia

text: Rhinovirus (RV) role in pathogenesis of severe childhood disease remains controversial. We aimed to explore the association between RV molecular subtyping, nasopharyngeal viral loads and viremia with childhood pneumonia. Nasopharyngeal and blood samples from cases and controls were tested for RV and the 5′ non-coding region sequenced. The cases compared to controls had a similar prevalence of RV detection in the nasopharynx (23 % vs. 22 %, P = 0.66), similar RV species distribution (A, B, C = 44 %, 8%, 44 % vs. 48 %, 7%, 38 %; respectively; P = 0.66) and similar viral load (4.0 and 3.7 log10 copies/mL, P = 0.062). However, RV-viremia was 4.01-fold (aOR 95 % CI: 1.26–12.78) more prevalent among cases (7%) than controls (2%), P = 0.019. Furthermore, among cases and controls RV-C was more commonly associated with viremia (14 % and 4%, P = 0.023), than RV-A (2% and 1%; P = 0.529). Thus RV-viremia could be used as a measure for attributing causality to RV in children hospitalized for pneumonia.


title: Chicken Interferon-Inducible Transmembrane Protein 3 Restricts Influenza Viruses and Lyssaviruses In Vitro

text: Interferon-inducible transmembrane protein 3 (IFITM3) is an effector protein of the innate immune system. It confers potent, cell-intrinsic resistance to infection by diverse enveloped viruses both in vitro and in vivo, including influenza viruses, West Nile virus, and dengue virus. IFITM3 prevents cytosolic entry of these viruses by blocking complete virus envelope fusion with cell endosome membranes. Although the IFITM locus, which includes IFITM1, -2, -3, and -5, is present in mammalian species, this locus has not been unambiguously identified or functionally characterized in avian species. Here, we show that the IFITM locus exists in chickens and is syntenic with the IFITM locus in mammals. The chicken IFITM3 protein restricts cell infection by influenza A viruses and lyssaviruses to a similar level as its human orthologue. Furthermore, we show that chicken IFITM3 is functional in chicken cells and that knockdown of constitutive expression in chicken fibroblasts results in enhanced infection by influenza A virus. Chicken IFITM2 and -3 are constitutively expressed in all tissues examined, whereas IFITM1 is only expressed in the bursa of Fabricius, gastrointestinal tract, cecal tonsil, and trachea. Despite being highly divergent at the amino acid level, IFITM3 proteins of birds and mammals can restrict replication of viruses that are able to infect different host species, suggesting IFITM proteins may provide a crucial barrier for zoonotic infections.


title: Crystal structure of the 2019-nCoV spike receptor-binding domain bound with the ACE2 receptor

text: A novel and highly pathogenic coronavirus (2019-nCoV) has caused an outbreak in Wuhan city, Hubei province of China since December 2019, and soon spread nationwide and spilled over to other countries around the world. To better understand the initial step of infection at atomic-level, we determined the crystal structure of the 2019-nCoV spike receptor-binding domain (RBD) bound with the cell receptor ACE2 at 2.45 Å resolution. The overall ACE2-binding mode of the 2019-nCoV RBD is nearly identical to that of the SARS-CoV RBD, which also utilizes ACE2 as the cell receptor. Structural analysis identified residues in 2019-nCoV RBD critical for ACE2 binding, and majority of which are either highly conserved or shared similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly argue for a convergent evolution between 2019-nCoV and SARS-CoV RBD for improved binding to ACE2 despite of being segregated in different genetic lineages in the betacoronavirus genus. The epitopes of two SARS-CoV antibodies targeting the RBD are also analyzed with the 2019-nCoV RBD, providing insights into future identification of cross-reactive antibodies.


title: A structural analysis of M protein in coronavirus assembly and morphology

text: The M protein of coronavirus plays a central role in virus assembly, turning cellular membranes into workshops where virus and host factors come together to make new virus particles. We investigated how M structure and organization is related to virus shape and size using cryo-electron microscopy, tomography and statistical analysis. We present evidence that suggests M can adopt two conformations and that membrane curvature is regulated by one M conformer. Elongated M protein is associated with rigidity, clusters of spikes and a relatively narrow range of membrane curvature. In contrast, compact M protein is associated with flexibility and low spike density. Analysis of several types of virus-like particles and virions revealed that S protein, N protein and genomic RNA each help to regulate virion size and variation, presumably through interactions with M. These findings provide insight into how M protein functions to promote virus assembly.


title: Replication of rat coronavirus in a rat cell line, LBC

text: Rat coronavirus readily propagated and induced marked cytopathic effect in a rat cell line, LBC cell culture, which provided a sensitive, practical assay system for viral infectivity and neutralizing antibody, and a satisfactory source of the virus.


title: Brief research report: Bidirectional impact of imperfect mask use on reproduction number of COVID-19: A next generation matrix approach()

text: The use of masks as a means of reducing transmission of COVID-19 outside healthcare settings has proved controversial. Masks are thought to have two modes of effect: they prevent infection with COVID-19 in wearers; and prevent transmission by individuals with subclinical infection. We used a simple next-generation matrix approach to estimate the conditions under which masks would reduce the reproduction number of COVID-19 under a threshold of 1. Our model takes into account the possibility of assortative mixing, where mask users interact preferentially with other mask users. We make 3 key observations: 1. Masks, even with suboptimal efficacy in both prevention of acquisition and transmission of infection, could substantially decrease the reproduction number for COVID-19 if widely used. 2. Widespread masking may be sufficient to suppress epidemics where R has been brought close to 1 via other measures (e.g., distancing). 3. “Assortment” within populations (the tendency for interactions between masked individuals to be more likely than interactions between masked and unmasked individuals) would rapidly erode the impact of masks. As such, mask uptake needs to be fairly universal to have an effect. This simple model suggests that widespread uptake of masking could be determinative in suppressing COVID-19 epidemics in regions with R(t) at or near 1.


title: Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase

text: Abstract As anti-HCV aryl diketoacids (ADK) are good metal chelators, we anticipated that ADKs might serve as potential inhibitors of SARS CoV (SCV) NTPase/helicase (Hel) by mimicking the binding modes of the bismuth complexes which effectively competes for the Zn2+ ion binding sites in SCV Hel thereby disrupting and inhibiting both the NTPase and helicase activities. Phosphate release assay and FRET-based assay of the ADK analogues showed that the ADKs selectively inhibit the duplex DNA-unwinding activity without significant impact on the helicase ATPase activity. Also, antiviral activities of the ADKs were shown dependent upon the substituent. Taken together, these results suggest that there might be ADK-specific binding site in the SCV Hel, which warrants further investigations with diverse ADKs to provide valuable insights into rational design of specific SCV Hel inhibitors.


title: Vaccinia virus F16 protein, a predicted catalytically inactive member of the prokaryotic serine recombinase superfamily, is targeted to nucleoli

text: Abstract The F16L gene of vaccinia virus (VACV) is conserved in all chordopoxviruses except avipoxviruses. The crocodile poxvirus F16 protein ortholog has highly significant similarity to prokaryotic serine recombinases and contains all amino acids that comprise the catalytic site. In contrast, F16 orthologs encoded by other poxviruses show only marginally significant similarity to serine recombinases, lack essential amino acids of the active site and are most likely inactive derivatives of serine recombinases. Nevertheless, the conservation of F16L in non-avian poxviruses suggested an important function. However, a VACV mutant with the F16L gene knocked out replicated normally in dividing and quiescent cells. The F16 protein was synthesized early after infection and detected in virus cores. When expressed in infected or uninfected cells, F16 accumulated in nucleoli depending on the level of expression and confluency of cells. Evidence was obtained that F16 forms multimers, which might regulate concentration-dependent intracellular localization.


title: On the Coronavirus (COVID-19) Outbreak and the Smart City Network: Universal Data Sharing Standards Coupled with Artificial Intelligence (AI) to Benefit Urban Health Monitoring and Management

text: As the Coronavirus (COVID-19) expands its impact from China, expanding its catchment into surrounding regions and other countries, increased national and international measures are being taken to contain the outbreak. The placing of entire cities in ‘lockdown’ directly affects urban economies on a multi-lateral level, including from social and economic standpoints. This is being emphasised as the outbreak gains ground in other countries, leading towards a global health emergency, and as global collaboration is sought in numerous quarters. However, while effective protocols in regard to the sharing of health data is emphasised, urban data, on the other hand, specifically relating to urban health and safe city concepts, is still viewed from a nationalist perspective as solely benefiting a nation’s economy and its economic and political influence. This perspective paper, written one month after detection and during the outbreak, surveys the virus outbreak from an urban standpoint and advances how smart city networks should work towards enhancing standardization protocols for increased data sharing in the event of outbreaks or disasters, leading to better global understanding and management of the same.


title: Analysis of complement deposition and viral RNA in placentas of COVID-19 patients

text: Abstract COVID-19, the disease caused by the novel Coronavirus, SARS-CoV-2, is increasingly being recognized as a systemic thrombotic and microvascular injury syndrome that may have its roots in complement activation. We had the opportunity to study the placental pathology of five full-term births to COVID-19 patients. All five exhibited histology indicative of fetal vascular malperfusion characterized by focal avascular villi and thrombi in larger fetal vessels. Vascular complement deposition in the placentas was not abnormal, and staining for viral RNA and viral spike protein was negative. While all cases resulted in healthy, term deliveries, these findings indicate the systemic nature of COVID-19 infection. The finding of vascular thrombosis without complement deposition may reflect the systemic nature of COVID-19's procoagulant effects unrelated to systemic complement activation.


Pain Management Best Practices from Multispecialty Organizations During the COVID-19 Pandemic and Public Health Crises—Evaluating the Risk of Infection Associated with Corticosteroid Injections


Preoperative SARS-CoV-2 screening: Can it really rule out COVID-19?


title: HIV-protease inhibitors block the replication of both vesicular stomatitis and influenza viruses at an early post-entry replication step

text: Abstract The inhibitors of HIV-1 protease (PIs) have been designed to block the activity of the viral aspartyl-protease. However, it is now accepted that this family of inhibitors can also affect the activity of cell proteases. Since the replication of many virus species requires the activity of host cell proteases, investigating the effects of PIs on the life cycle of viruses other than HIV would be of interest. Here, the potent inhibition induced by saquinavir and nelfinavir on the replication of both vesicular stomatitis and influenza viruses is described. These are unrelated enveloped RNA viruses infecting target cells upon endocytosis and intracellular fusion. The PI-induced inhibition was apparently a consequence of a block at the level of the fusion between viral envelope and endosomal membranes. These findings would open the way towards the therapeutic use of PIs against enveloped RNA viruses other than HIV.


title: Change in bacterial aetiology of peritoneal dialysis-related peritonitis over 10 years: experience from a centre in south-east Asia

text: ABSTRACT This study reviewed 1787 episodes of peritoneal dialysis (PD)-related peritonitis in 544 patients between 1994 and 2003. The overall rate of peritonitis was 0.68 episodes/year of PD, but decreased from 1.10 to 0.46 episodes/year between 1994 and 2003. The incidence of peritonitis caused by coagulase-negative staphylococci declined between 1994 and 1998 from 0.21 to 0.06 episodes/year of PD, coinciding with a reduction in the use of spike PD sets. There was a 60.1% response rate to antibiotics throughout the period, but the percentage of cases that required modification of the initial empirical antibiotic regimen rose from 13.6% to 58.7%, indicating that treatment should be individualised.


title: Mouse hepatitis virus pathogenesis in the central nervous system is independent of IL-15 and natural killer cells

text: Abstract Infection by the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in an acute encephalomyelitis associated with demyelination. T cells are critical in controlling viral replication, but also contribute to central nervous system (CNS) pathogenesis. To reveal a role for innate effectors in anti-viral immunity and neurological disease, JHMV pathogenesis was studied in mice deficient in interleukin-15 (IL-15−/−) and natural killer (NK) cells. Clinical disease, CNS inflammation and demyelination in infected IL-15−/− mice were similar to wild-type mice. Despite the absence of NK cells and suboptimal CD8+ T cell responses, IL-15−/− mice controlled JHMV replication as efficiently as wild-type mice. Similar kinetics of class I and class II upregulation on microglia further suggested no role of NK cells in regulating major histocompatibility complex (MHC) molecule expression on resident CNS cells. IL-15 and NK cells thus appear dispensable for anti-viral immunity and CNS pathogenesis during acute JHMV infection.


title: Clinical Description of a Completed Outbreak of SARS in Vietnam, February–May, 2003

text: We investigated the clinical manifestations and course of all probable severe acute respiratory syndrome (SARS) patients in the Vietnam outbreak. Probable SARS cases were defined by using the revised World Health Organization criteria. We systematically reviewed medical records and undertook descriptive statistical analyses. All 62 patients were hospitalized. On admission, the most prominent symptoms were malaise (82.3%) and fever (79.0%). Cough, chest pain, and shortness of breath were present in approximately one quarter of the patients; 79.0% had lymphopenia; 40.3% had thrombocytopenia; 19.4% had leukopenia; and 75.8% showed changes on chest radiograph. Fever developed on the first day of illness onset, and both respiratory symptoms and radiographic changes occurred on day 4. On average, maximal radiographic changes were observed on day 10, and fevers subsided by day 13. Symptoms on admission were nonspecific, although fever, malaise, and lymphopenia were common. The complications of SARS included invasive intubation and ventilation (11.3%) and death (9.7%).


title: Travelers as a sentinel population: Use of sentinel networks to inform pretravel and posttravel evaluation

text: The establishment of collaborative sentinel surveillance networks specifically to monitor disease trends among travelers offers new options for evaluating travel health issues. These networks can inform preand posttravel patient management by providing complementary surveillance information, facilitating communication and collaboration between participating network sites, and enabling new analytical options for travel-related research. The two major multinational sentinel networks are TropNetEurop and GeoSentinel. Practical examples demonstrating their significant contributions to improved travel health information are discussed. Data obtained from studying health problems among travelers may also have significant benefits for local populations in resource-limited countries. However, there are limitations of data collected by sentinel networks, so they should be considered as complementary tools and not relied on as an exclusive basis for evaluating health risks among travelers.


title: Endogenous IL‐12 synthesis is not required to prevent hyperexpression of type 2 cytokine and antibody responses

text: Endogenous IL‐12 production is hypothesized to play an essential role preventing spontaneous expression of type 2 responses, acting as a natural inhibitor limiting development of immediate hypersensitivity. Here, IL‐12‐deficient p35(– / –) and p40(– / –) mice were used to examine the role of endogenous IL‐12 and p40 homodimer during in vivo development of exogenous antigen‐driven responses. In the absence of deliberate immunization, IL‐12‐deficient mice exhibited greatly reduced serum IgG2a but IgG1 / IgE levels no higher than controls. Immunization to elicit polarized ovalbumin‐specific type 1 or type 2 dominant responses, or using Trichinella spiralis extract in the absence of adjuvants, led to IFN‐γ production of approximately 10 % of C57BL / 6 controls yet the kinetics and intensity of primary and secondary type 2 cytokine (IL‐4, IL‐5, IL‐13) and antibody (IgG1, IgE) responses, as well as functional IL‐12 receptor expression, were consistently unaltered. Thus, while IL‐12 provides an important positive signal for Th1 development, antigen exposure in its absence does not lead to generalized enhancement of type 2 cytokine or antibody responses. The data argue that endogenous IL‐12 production is not required as a constitutive negative regulator limiting induction or expression of type 2 effector responses.


Under the coronavirus disease 2019(COVID-19) pandemic circumstance, how to administrate cancer patients with fever during radiotherapy


title: The E Protein Is a Multifunctional Membrane Protein of SARS-CoV

text: The E (envelope) protein is the smallest structural protein in all coronaviruses and is the only viral structural protein in which no variation has been detected. We conducted genome sequencing and phylogenetic analyses of SARS-CoV. Based on genome sequencing, we predicted the E protein is a transmembrane (TM) protein characterized by a TM region with strong hydrophobicity and α-helix conformation. We identified a segment (NH(2)-_L-Cys-A-Y-Cys-Cys-N_-COOH) in the carboxyl-terminal region of the E protein that appears to form three disulfide bonds with another segment of corresponding cysteines in the carboxyl-terminus of the S (spike) protein. These bonds point to a possible structural association between the E and S proteins. Our phylogenetic analyses of the E protein sequences in all published coronaviruses place SARS-CoV in an independent group in Coronaviridae and suggest a non-human animal origin.


title: Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis

text: The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver.


title: Data for understanding the risk perception of COVID-19 from Vietnamese sample

text: This data article describes the risk perception of COVID-190 from 391 Vietnamese respondents aged from 15 to 47 years. These data have been used in Huynh (2020). These data include the socioeconomics, media attention, and risk perception of COVID-19 in Vietnam through a survey conducted on February 1, 2020. In addition, our data might serve as a reference source for further in-depth surveys to understand the risk perception and social media communication across countries.


The impact of COVID‐19 on Head and Neck surgery, education, and training


title: Crystallization and preliminary crystallographic analysis of the fusion core of the spike protein of the murine coronavirus mouse hepatitis virus (MHV)

text: Crystals of a 2‐Helix fusion‐core construct of MHV spike protein (commonly referred to as E2) have been grown at 291 K using PEG 4000 as precipitant. The diffraction pattern of the crystal extends to 2.8 Å resolution at 100 K in‐house. Furthermore, a selenomethionine (SeMet) derivative of MHV spike protein fusion core has been overexpressed and purified. The derivative crystals were obtained under similar conditions and three different wavelength data sets were collected to 2.4 Å resolution from a single derivative crystal at BSRF (Beijing Synchrotron Radiation Facility). The crystals have unit‐cell parameters a = b = 48.3, c = 199.6 Å, α = β = 90, γ = 120° and belong to space group R3. Assuming the presence of two molecules in the asymmetric unit, the solvent content is calculated to be about 46%.


title: Genomic instability and rapid clinical course in adult T-cell lymphoma/leukemia patient

text: Abstract Adult T-cell leukemia/lymphoma is a distinct clinical entity characterized by a clonal proliferation of malignant T-lymphocytes. The etiologic agent of the disease is a Human T-cell lymphotropic virus type I. It occurs almost exclusively in areas where the virus is endemic; however the disease develops only in the minority of patients who are virus carriers. Karyotyping findings and their correlation with clinical features are still limited in T-cell malignancies, complicated by clinical heterogeneity and a plethora of secondary abnormalities. This study describes detailed chromosomal and fluorescence in situ hybridization results observed in a patient with adult T-cell leukemia/lymphoma and correlates them with clinical characteristics.


title: The hemagglutinin/esterase gene of human coronavirus strain OC43: Phylogenetic relationships to bovine and murine coronaviruses and influenza C virus

text: Abstract The complete nucleotide sequences of the hemagglutinin/esterase (HE) genes of human coronavirus (HCV) strain OC43 and bovine respiratory coronavirus (BRCV) strain G95 were determined from single-stranded cDNA fragments generated by reverse transcription of virus-specific mRNAs and amplified by polymerase chain reaction. An open reading frame of 1272 nucleotides was identified as the putative HE gene by homology to the bovine coronavirus HE gene. This open reading frame encodes a protein of 424 amino acids with an estimated molecular weight of 47.7 kDa. Ten potential N-linked glycosylation sites were predicted in the HE protein of HCV-OC43 while nine of them were present in BRCV-G95. Fourteen cysteine residues were conserved in the HE proteins of both viruses. Two hydrophobic sequences at the N-terminus and the C-terminus may serve as signal peptide and transmembrane anchoring domain, respectively. The predicted HE protein of HCV-OC43 was 95% identical to the HEs of BRCV-G95 and other bovine coronaviruses, and 60% identical to the HEs of mouse hepatitis viruses. Phylogenetic analysis suggests that the HE genes of coronaviruses and influenza C virus have a common ancestral origin, and that bovine coronaviruses and HCV-OC43 are closely related.


title: Vaccines as alternatives to antibiotics for food producing animals. Part 2: new approaches and potential solutions

text: Vaccines and other alternative products are central to the future success of animal agriculture because they can help minimize the need for antibiotics by preventing and controlling infectious diseases in animal populations. To assess scientific advancements related to alternatives to antibiotics and provide actionable strategies to support their development, the United States Department of Agriculture, with support from the World Organisation for Animal Health, organized the second International Symposium on Alternatives to Antibiotics. It focused on six key areas: vaccines; microbial-derived products; non-nutritive phytochemicals; immune-related products; chemicals, enzymes, and innovative drugs; and regulatory pathways to enable the development and licensure of alternatives to antibiotics. This article, the second part in a two-part series, highlights new approaches and potential solutions for the development of vaccines as alternatives to antibiotics in food producing animals; opportunities, challenges and needs for the development of such vaccines are discussed in the first part of this series. As discussed in part 1 of this manuscript, many current vaccines fall short of ideal vaccines in one or more respects. Promising breakthroughs to overcome these limitations include new biotechnology techniques, new oral vaccine approaches, novel adjuvants, new delivery strategies based on bacterial spores, and live recombinant vectors; they also include new vaccination strategies in-ovo, and strategies that simultaneously protect against multiple pathogens. However, translating this research into commercial vaccines that effectively reduce the need for antibiotics will require close collaboration among stakeholders, for instance through public–private partnerships. Targeted research and development investments and concerted efforts by all affected are needed to realize the potential of vaccines to improve animal health, safeguard agricultural productivity, and reduce antibiotic consumption and resulting resistance risks.


title: Computational View toward the Inhibition of SARS-CoV-2 Spike Glycoprotein and the 3CL Protease

text: Since the outbreak of the 2019 novel coronavirus disease (COVID-19), the medical research community is vigorously seeking a treatment to control the infection and save the lives of severely infected patients. The main potential candidates for the control of viruses are virally targeted agents. In this short letter, we report our calculations on the inhibitors for the SARS-CoV-2 3CL protease and the spike protein for the potential treatment of COVID-19. The results show that the most potent inhibitors of the SARS-CoV-2 3CL protease include saquinavir, tadalafil, rivaroxaban, sildenafil, dasatinib, etc. Ergotamine, amphotericin b, and vancomycin are most promising to block the interaction of the SARS-CoV-2 S-protein with human ACE-2.


title: Inactivation of an enterovirus by airborne disinfectants

text: BACKGROUND: The activity of airborne disinfectants on bacteria, fungi and spores has been reported. However, the issue of the virucidal effect of disinfectants spread by fogging has not been studied thoroughly. METHODS: A procedure has been developed to determine the virucidal activity of peracetic acid-based airborne disinfectants on a resistant non-enveloped virus poliovirus type 1. This virus was laid on a stainless carrier. The products were spread into the room by hot fogging at 55°C for 30 minutes at a concentration of 7.5 mL.m(-3). Poliovirus inoculum, supplemented with 5%, heat inactivated non fat dry organic milk, were applied into the middle of the stainless steel disc and were dried under the air flow of a class II biological safety cabinet at room temperature. The Viral preparations were recovered by using flocked swabs and were titered on Vero cells using the classical Spearman-Kärber CPE reading method, the results were expressed as TCID50.ml(-1). RESULTS: The infectious titer of dried poliovirus inocula was kept at 10(5) TCID(50).mL(-1) up to 150 minutes at room temperature. Dried inocula exposed to airborne peracetic acid containing disinfectants were recovered at 60 and 120 minutes post-exposition and suspended in culture medium again. The cytotoxicity of disinfectant containing medium was eliminated through gel filtration columns. A 4 log reduction of infectious titer of dried poliovirus inocula exposed to peracetic-based airborne disinfectant was obtained. CONCLUSION: This study demonstrates that the virucidal activity of airborne disinfectants can be tested on dried poliovirus.


title: Chikungunya triggers an autophagic process which promotes viral replication

text: BACKGROUND: Chikungunya Virus (ChikV) surprised by a massive re-emerging outbreak in Indian Ocean in 2006, reaching Europe in 2007 and exhibited exceptional severe physiopathology in infants and elderly patients. In this context, it is important to analyze the innate immune host responses triggered against ChikV. Autophagy has been shown to be an important component of the innate immune response and is involved in host defense elimination of different pathogens. However, the autophagic process was recently observed to be hijacked by virus for their own replication. Here we provide the first evidence that hallmarks of autophagy are specifically found in HEK.293 infected cells and are involved in ChikV replication. METHODS: To test the capacity of ChikV to mobilize the autophagic machinery, we performed fluorescence microscopy experiments on HEK.GFP.LC3 stable cells, and followed the LC3 distribution during the time course of ChikV infection. To confirm this, we performed electron microscopy on HEK.293 infected cells. To test the effect of ChikV-induced-autophagy on viral replication, we blocked the autophagic process, either by pharmacological (3-MA) or genetic inhibition (siRNA against the transcript of Beclin 1, an autophagic protein), and analyzed the percentage of infected cells and the viral RNA load released in the supernatant. Moreover, the effect of induction of autophagy by Rapamycin on viral replication was tested. RESULTS: The increasing number of GFP-LC3 positive cells with a punctate staining together with the enhanced number of GFP-LC3 dots per cell showed that ChikV triggered an autophagic process in HEK.293 infected cells. Those results were confirmed by electron microscopy analysis since numerous membrane-bound vacuoles characteristic of autophagosomes were observed in infected cells. Moreover, we found that inhibition of autophagy, either by biochemical reagent and RNA interference, dramatically decreases ChikV replication. CONCLUSIONS: Taken together, our results suggest that autophagy may play a promoting role in ChikV replication. Investigating in details the relationship between autophagy and viral replication will greatly improve our knowledge of the pathogenesis of ChikV and provide insight for the design of candidate antiviral therapeutics.


title: Recent advances in live cell imaging of hepatoma cells

text: Live cell imaging enables the study of dynamic processes of living cells in real time by use of suitable reporter proteins and the staining of specific cellular structures and/or organelles. With the availability of advanced optical devices and improved cell culture protocols it has become a rapidly growing research methodology. The success of this technique relies mainly on the selection of suitable reporter proteins, construction of recombinant plasmids possessing cell type specific promoters as well as reliable methods of gene transfer. This review aims to provide an overview of the recent developments in the field of marker proteins (bioluminescence and fluorescent) and methodologies (fluorescent resonance energy transfer, fluorescent recovery after photobleaching and proximity ligation assay) employed as to achieve an improved imaging of biological processes in hepatoma cells. Moreover, different expression systems of marker proteins and the modes of gene transfer are discussed with emphasis on the study of lipid droplet formation in hepatocytes as an example.


title: Antibacterial activity evaluation of selected essential oils in liquid and vapor phase on respiratory tract pathogens

text: BACKGROUND: The increasing number of multidrug-resistant bacteria and the fact of antibiotic resistance is leading to a continuous need for discovering alternative treatments against infections, e.g. in the case of respiratory tract diseases. Essential oils (EOs), because of their volatility, can easily reach both the upper and lower parts of the respiratory tract via inhalation. Therefore, the aim of the present study was the antibacterial evaluation of clove, cinnamon bark, eucalyptus, thyme, scots pine, peppermint, and citronella EOs against respiratory tract pathogens such as Streptococcus pneumoniae, S. mutans, S. pyogenes, Haemophilus influenzae, H. parainfluenzae, and Moraxella catarrhalis. Furthermore, we wanted to compare the antibacterial effect of these EOs in two different test systems to provide data for the development of an appropriate product formulation. METHODS: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined with in vitro vapor phase test (VPT) and broth macrodilution test (BDT). The chemical and percentage compositions of the EOs were determined by GC-MS and GC-FID analysis. RESULTS: Among the EOs, thyme was the most effective against S. mutans (MIC: 0.04 mg/mL in BDT, but cinnamon bark and clove oils also presented high inhibition in liquid medium with MIC values of 0.06 mg/mL and 0.1 mg/mL against S. pneumoniae and S. pyogenes, respectively. M. catarrhalis was the most sensitive to thyme EO (MIC: 0.09 mg/mL). Cinnamon bark EO was the most effective against Haemophilus spp. (MIC: 0.06 mg/mL). In the VPT, cinnamon bark was the most effective oil against all investigated pathogens with MIC values in the range of 15.62–90 μl/L. Surprisingly, the eucalyptus and scots pine showed weak activity against the test bacteria in both test systems. CONCLUSIONS: The EO of thyme, clove and cinnamon bark may provide promising antibacterial activity against respiratory tract pathogens either in liquid medium or in vapor phase. However, their effect is lower than that of the reference antibiotics. The combination of EOs and antibiotics may be beneficial in the alternative treatment of respiratory tract diseases. In vivo studies are necessary to calculate the effective dose of EOs in patients and determine their possible side effects and toxicity.


A review of the impact of Covid‐19 corona virus on the oil sector


title: A snapshot of pneumonia research activity and collaboration patterns (2001–2015): a global bibliometric analysis

text: BACKGROUND: This article describes a bibliometric review of the scientific production, geographical distribution, collaboration, impact, and subject area focus of pneumonia research indexed on the Web of Science over a 15-year period. METHODS: We searched the Web of Science database using the Medical Subject Heading (MeSH) of “Pneumonia” from January 1, 2001 to December 31, 2015. The only document types we studied were original articles and reviews, analyzing descriptive indicators by five-year periods and the scientific production by country, adjusting for population, economic, and research-related parameters. RESULTS: A total of 22,694 references were retrieved. The number of publications increased steadily over time, from 981 publications in 2001 to 1977 in 2015 (R(2) = 0.956). The most productive country was the USA (38.49%), followed by the UK (7.18%) and Japan (5.46%). Research production from China increased by more than 1000%. By geographical area, North America (42.08%) and Europe (40.79%) were most dominant. Scientific production in low- and middle-income countries more than tripled, although their overall contribution to the field remained limited (< 15%). Overall, 18.8% of papers were the result of an international collaboration, although this proportion was much higher in sub-Saharan Africa (46.08%) and South Asia (23.43%). According to the specific MeSH terms used, articles focused mainly on “Pneumonia, Bacterial” (19.99%), followed by “Pneumonia, Pneumococcal” (7.02%) and “Pneumonia, Ventilator-Associated” (6.79%). CONCLUSIONS: Pneumonia research increased steadily over the 15-year study period, with Europe and North America leading scientific production. About a fifth of all papers reflected international collaborations, and these were most evident in papers from sub-Saharan Africa and South Asia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12874-019-0819-4) contains supplementary material, which is available to authorized users.


Veneto's successful lesson for a world shocked by COVID-19: think globally and act locally


Severe acute respiratory syndrome: review and lessons of the 2003 outbreak


title: Glycosylation of viral surface proteins probed by mass spectrometry

text: Glycosylation is a common and biologically significant post-translational modification that is found on numerous virus surface proteins (VSPs). Many of these glycans affect virulence through modulating virus receptor binding, masking antigenic sites, or by stimulating the host immune response. Mass spectrometry (MS) has arisen as a pivotal technique for the characterization of VSP glycosylation. This review will cover how MS-based analyses, such as released glycan profiles, glycan site localization, site-occupancy, and site-specific heterogeneity, are being utilized to map VSP glycosylation. Furthermore, this review will provide information on how MS glycoprofiling data are being used in conjunction with molecular and structural experiments to provide a better understanding of the role of specific glycans in VSP function.


title: High-Dose Oral Erythromycin Decreased the Incidence of Parenteral Nutrition-Associated Cholestasis in Preterm Infants

text: Background & Aims: Feeding intolerance because of functional gastrointestinal dysmotility and parenteral nutrition-associated cholestasis (PNAC) are common problems in preterm, very-low-birth-weight (VLBW) infants. This double-blind, randomized, placebo-controlled study aimed to assess the effectiveness of “high-dose” oral erythromycin as a prokinetic agent in decreasing the incidence of PNAC. Two secondary end points, including the time to achieve full enteral feeding and the duration of parenteral nutrition, were also evaluated. Methods: Infants consecutively admitted to the neonatal unit were randomized to receive erythromycin (12.5 mg/kg/dose every 6 hours for 14 days) or an equivalent volume of normal saline (placebo) if they attained less than half the total daily fluid intake (<75 mL/kg/day) as milk feeds on day 14 of life. Results: Of 182 VLBW infants enrolled, 91 received erythromycin. The incidence of PNAC was significantly lower in erythromycin-treated infants (18/91) compared with placebo infants (37/91; P = .003). Treated infants achieved full enteral nutrition significantly earlier (mean, 10.1; SE, 1.7 days; P < .001), and the duration of parenteral nutrition was also significantly decreased by 10 days (P < .001). Importantly, fewer infants receiving erythromycin had 2 or more episodes of septicemia (n = 4) compared with placebo patients (n = 13, P = .03). No serious adverse effect was associated with erythromycin treatment. Conclusions: High-dose oral erythromycin can be considered as a rescue measure for VLBW infants who fail to establish adequate enteral nutrition and in whom anatomically obstructive pathologies of the gastrointestinal tract have been excluded.


title: Antiviral Phosphorodiamidate Morpholino Oligomers are Protective against Chikungunya Virus Infection on Cell-based and Murine Models

text: Chikungunya virus (CHIKV) infection in human is associated with debilitating and persistent arthralgia and arthritis. Currently, there is no specific vaccine or effective antiviral available. Anti-CHIKV Phosphorodiamidate Morpholino Oligomer (CPMO) was evaluated for its antiviral efficacy and cytotoxcity in human cells and neonate murine model. Two CPMOs were designed to block translation initiation of a highly conserved sequence in CHIKV non-structural and structural polyprotein, respectively. Pre-treatment of HeLa cells with CPMO1 signficantly suppressed CHIKV titre, CHIKV E2 protein expression and prevented CHIKV-induced CPE. CPMO1 activity was also CHIKV-specific as shown by the lack of cross-reactivity against SINV or DENV replication. When administered prophylactically in neonate mice, 15 μg/g CPMO1v conferred 100% survival against CHIKV disease. In parallel, these mice demonstrated significant reduction in viremia and viral load in various tissues. Immunohistological examination of skeletal muscles and liver of CPMO1v-treated mice also showed healthy tissue morphology, in contrast to evident manifestation of CHIKV pathogenesis in PBS- or scrambled sCPMO1v-treated groups. Taken together, our findings highlight for the first time that CPMO1v has strong protective effect against CHIKV infection. This warrants future development of morpholino as an alternative antiviral agent to address CHIKV infection in clinical applications.


title: Epidemiological analysis of respiratory viral etiology for influenza-like illness during 2010 in Zhuhai, China

text: BACKGROUND: Influenza-like illnesses (ILI), a subset of acute respiratory infections (ARI), are a significant source of morbidity and mortality worldwide. ILI can be caused by numerous pathogens, however; there is limited information on the etiology and epidemiology of ILI in China. METHODS: We performed a one-year surveillance study (2010) of viral etiology causing ILI and investigated the influence of climate on outbreaks of ILI attributed to viruses at the Outpatient Department of Zhuhai Municipal People’s Hospital in Zhuhai, China. RESULTS: Of the 337,272 outpatients who sought attention in the Outpatient Department of Zhuhai Municipal People’s Hospital in 2010, 3,747 (1.11%) presented with ILI. Of these patients presenting with ILI, 24.66% (924/3,747) had available samples and were enrolled in this study. At least one respiratory virus was identified in 411 patients (44.48%) and 42 (4.55%) were co-infected with two viruses. In patients co-infected with two viruses, respiratory syncytial virus (RSV) was detected in 50% (21/42). Among common viral pathogens detected, significant differences in age distributions were observed in seasonal influenza virus A (sFulA, H3N2) and B (sFluB), pandemic H1N1 2009 influenza viruses (H1N1pdm09), RSV, and adenovirus (ADV). Infections with sFluA (H3N2), sFluB, RSV, and human metapneumovirus (HMPV) had characteristic seasonal patterns. The incidences of sFluA (H3N2), ADV, and RSV correlated with air temperature. Alternatively, the incidence of sFluB correlated with relative air humidity. CONCLUSIONS: These results demonstrate that a wide range of respiratory viral pathogens are circulating in Zhuhai city. This information needs to be considered by clinicians when treating patients presenting with ILI.


Failure Modes and Effect Analysis to develop transfer protocols in the management of COVID-19 patients


title: Susceptibility of five strains of Cryptosporidium parvum oocysts to UV light

text: Previous evaluations of the effect of ultraviolet (UV) light on Cryptosporidium parvum oocysts have been limited to a single strain—the Iowa strain. This study investigated the response of five strains of C. parvum to UV. A collimated beam apparatus was used to apply controlled doses of monochromatic (254 nm) UV to oocysts of the Iowa, Moredun, Texas A&M, Maine, and Glasgow strains. Irradiation was measured using a calibrated radiometer and sensor. Inactivation was quantified through animal infectivity by inoculation of cohorts of CD‐1 neonatal mice with UV‐treated and untreated control oocysts of each strain followed by examination of intestinal sections for infection using hemotoxylin and eosin staining. A UV light dose of 10 mJ/cm(2) achieved at least 4‐log(10) inactivation of all strains evaluated. All five strains of C. parvum were shown to be highly susceptible to low levels of UV light.


title: Management of acute and chronic respiratory tract infections

text: Abstract Pharyngitis, bronchitis, and pneumonia represent the most common respiratory tract infections. With a view to establishing effective management strategies, the origins of these illnesses and the diagnostic techniques that have been developed to discover them are reviewed. Therapeutic regimens with documented efficacy are outlined with emphasis on specific rather than empiric treatment. Although many respiratory tract pathogens remain exquisitely sensitive to penicillin, the emergence of resistant strains underscores the need for safe and effective alternative therapies.


Editor's perspective: COVID‐19's impact on the remediation industry


title: Diagnosing and preventing chronic suppurative lung disease (CSLD) and bronchiectasis

text: Summary Current diagnostic labelling of childhood bronchiectasis by radiology has substantial limitations. These include the requirement for two high resolution computerised tomography [HRCT] scans (with associated adversity of radiation) if criteria is adhered to, adoption of radiological criteria for children from adult data, relatively high occurrence of false negative, and to a smaller extent false positive, in conventional HRCT scans when compared to multi-detector CT scans, determination of irreversible airway dilatation, and absence of normative data on broncho-arterial ratio in children. A paradigm presenting a spectrum related to airway bacteria, with associated degradation and inflammation products causing airway damage if untreated, entails protracted bacterial bronchitis (at the mild end) to irreversible airway dilatation with cystic formation as determined by HRCT (at the severe end of the spectrum). Increasing evidence suggests that progression of airway damage can be limited by intensive treatment, even in those predestined to have bronchiectasis (eg immune deficiency). Treatment is aimed at achieving a cure in those at the milder end of the spectrum to limiting further deterioration in those with severe ‘irreversible’ radiological bronchiectasis.


Acute Care Surgeons’ Response to the COVID-19 Pandemic: Observations and Strategies from the Epicenter of the American Crisis


title: Viral intestinal infections of animals and man

text: Abstract The extensive use of negative staining techniques and electron microscopy in diagnostic centers has resulted in a dramatic increase in the number of reported viral enteric infections in man and animals in the last 10 yr. Enteric infection due to adenoviruses, astroviruses, coronaviruses, paramyxoviruses, parvoviruses, picornaviruses (caliciviruses), rotaviruses as well as some unidentified viral particles are described. The brief literature review on each of these virus families is supplemented with clinical cases submitted to the Texas Veterinary Medical Diagnostic Laboratory. Comparative aspects of viral infections between different animal species as well as man are discussed wherever possible.


title: Targeting Cell Entry of Enveloped Viruses as an Antiviral Strategy

text: The entry of enveloped viruses into their host cells involves several successive steps, each one being amenable to therapeutic intervention. Entry inhibitors act by targeting viral and/or cellular components, through either the inhibition of protein-protein interactions within the viral envelope proteins or between viral proteins and host cell receptors, or through the inhibition of protein-lipid interactions. Interestingly, inhibitors that concentrate into/onto the membrane in order to target a protein involved in the entry process, such as arbidol or peptide inhibitors of the human immunodeficiency virus (HIV), could allow the use of doses compatible with therapeutic requirements. The efficacy of these drugs validates entry as a point of intervention in viral life cycles. Strategies based upon small molecule antiviral agents, peptides, proteins or nucleic acids, would most likely prove efficient in multidrug combinations, in order to inhibit several steps of virus life cycle and prevent disease progression.


title: The population genetics of drug resistance evolution in natural populations of viral, bacterial and eukaryotic pathogens

text: Drug resistance is a costly consequence of pathogen evolution and a major concern in public health. In this review, we show how population genetics can be used to study the evolution of drug resistance and also how drug resistance evolution is informative as an evolutionary model system. We highlight five examples from diverse organisms with particular focus on: (i) identifying drug resistance loci in the malaria parasite Plasmodium falciparum using the genomic signatures of selective sweeps, (ii) determining the role of epistasis in drug resistance evolution in influenza, (iii) quantifying the role of standing genetic variation in the evolution of drug resistance in HIV, (iv) using drug resistance mutations to study clonal interference dynamics in tuberculosis and (v) analysing the population structure of the core and accessory genome of Staphylococcus aureus to understand the spread of methicillin resistance. Throughout this review, we discuss the uses of sequence data and population genetic theory in studying the evolution of drug resistance.


title: Infectious Agents Detected in the Feces of Diarrheic Foals: A Retrospective Study of 233 Cases (2003–2008)

text: Background: Diarrhea is common in foals but there are no studies investigating the relative prevalence of common infectious agents in a population of hospitalized diarrheic foals. Objectives: To determine the frequency of detection of infectious agents in a population of hospitalized foals with diarrhea and to determine if detection of specific pathogens is associated with age, outcome, or clinicopathologic data. Animals: Two hundred and thirty‐three foals ≤ 10 months of age with diarrhea examined at a referral institution. Methods: Retrospective case series. Each foal was examined for Salmonella spp., viruses, Clostridium difficile toxins, Clostridium perfringens culture, C. perfringens enterotoxin, Cryptosporidium spp., and metazoan parasites in feces collected at admission or at the onset of diarrhea. Results: At least 1 infectious agent was detected in 122 foals (55%). Rotavirus was most frequently detected (20%) followed by C. perfringens (18%), Salmonella spp. (12%), and C. difficile (5%). Foals < 1 month of age were significantly more likely to be positive for C. perfringens (odds ratio [OR] = 15, 95% confidence interval [CI] = 3.5–66) or to have negative fecal diagnostic results (OR = 3.0, 95% CI = 1.7–5.2) than older foals. Foals > 1 month of age were significantly more likely to have Salmonella spp. (OR = 2.6, 95% CI = 1.2–6.0), rotavirus (OR = 13.3, 95% CI = 5.3–33), and parasites (OR = 23, 95% CI = 3.1–185) detected compared with younger foals. Overall 191 of the 223 foals (87%) survived. The type of infectious agent identified in the feces or bacteremia was not significantly associated with survival. Conclusions and Clinical Importance: In the population studied, foals with diarrhea had a good prognosis regardless of which infectious agent was identified in the feces.


title: 优化解决肺癌患者在新型冠状病毒肺炎疫情期间诊疗问题及心理问题的探索

text: BACKGROUND AND OBJECTIVE: With the rapid spread of novel coronavirus pneumonia (NCP) worldwide and the escalation of prevention and control efforts, the routine medical needs of patients have been restricted. The aims were to investigate medical needs of lung cancer patients and their mental health status during the epidemic periods, so as to provide rational recommendations for subsequent diagnosis and treatment. METHODS: The questionnaire was sent in the form of an electronic questionnaire at 7am on 4(th), March, 2020, until 7am 6(th), March, 2020, 368 questionnaires were recollected from 25 provinces (autonomous regions/municipalities) in 48 h. RESULTS: Of the 368 patients, 18 patients were excluded as they didn't receive anti-tumor treatment, and 350 patients were included in the final analysis. 229 cases were treated with oral targeted drugs, and 121 cases were treated with chemotherapy or immunotherapy. 41.3% of patients treated with intravenous chemotherapy or immunotherapy experienced treatment discontinuation, and the proportion of treatment discontinuation in chemotherapy or immunotherapy was higher than those treated with oral targeted drugs (21.0%). Whether oral targeted drugs or intravenous chemotherapy or immunotherapy, more than 60% of patients experienced delays in imaging examinations. Nearly one third of patients developed new symptoms or exacerbation of existing symptoms. 26.6%-28.9% of patients have changed their treatment plans through online consultation. During novel coronavirus pneumonia, 40%-75% of lung cancer patients have mental health problems, and more than 95% of patients support government's prevention and control measures. CONCLUSIONS: During the emergence of NCP, the medical needs of patients with lung cancer have not been enough, especially those who discontinued chemotherapy or immunotherapy. When medical institution resumes work, priority should be given to them. At the same time, mental health problems of patients should be valued and resolved timely.


title: Hospice utilization during the SARS outbreak in Taiwan

text: BACKGROUND: The severe acute respiratory syndrome (SARS) epidemic threw the world into turmoil during the first half of 2003. Many subsequent papers have addressed its impact on health service utilization, but few have considered palliative (hospice) care. The aim of the present study was to describe changes in hospice inpatient utilization during and after the SARS epidemic in 2003 in Taiwan. METHODS: The data sources were the complete datasets of inpatient admissions during 2002 and 2003 from the National Health Insurance Research Database. Before-and-after comparisons of daily and monthly utilizations were made. Hospice analyses were limited to those wards that offered inpatient services throughout these two years. The comparisons were extended to total hospital bed utilization and to patients who were still admitted to hospice wards during the peak period of the SARS epidemic. RESULTS: Only 15 hospice wards operated throughout the whole of 2002 and 2003. In 2003, hospice utilization began to decrease in the middle of April, reached a minimum on 25 May, and gradually recovered to the level of the previous November. Hospices showed a more marked reduction in utilization than all hospital beds (e.g. -52.5% vs. -19.9% in May 2003) and a slower recovery with a three-month lag. In total, 566 patients were admitted to hospice wards in May/June 2003, in contrast to 818 in May/June 2002. Gender, age and diagnosis distributions did not differ. CONCLUSION: Hospice inpatient utilization in Taiwan was indeed more sensitive to the emerging epidemic than general inpatient utilization. A well-balanced network with seamless continuity of care should be ensured.