title: Involvement of lipid microdomains in human endothelial cells infected by Streptococcus agalactiae type III belonging to the hypervirulent ST-17

text: BACKGROUND: Streptococcus agalactiae capsular type III strains are a leading cause of invasive neonatal infections. Many pathogens have developed mechanisms to escape from host defense response using the host membrane microdomain machinery. Lipid rafts play an important role in a variety of cellular functions and the benefit provided by interaction with lipid rafts can vary from one pathogen to another. OBJECTIVES: This study aims to evaluate the involvement of membrane microdomains during infection of human endothelial cell by S. agalactiae. METHODS: The effects of cholesterol depletion and PI3K/AKT signaling pathway activation during S. agalactiae-human umbilical vein endothelial cells (HUVEC) interaction were analysed by pre-treatment with methyl-β-cyclodextrin (MβCD) or LY294002 inhibitors, immunofluorescence and immunoblot analysis. The involvement of lipid rafts was analysed by colocalisation of bacteria with flotillin-1 and caveolin-1 using fluorescence confocal microscopy. FINDINGS: In this work, we demonstrated the importance of the integrity of lipid rafts microdomains and activation of PI3K/Akt pathway during invasion of S. agalactiae strain to HUVEC cells. Our results suggest the involvement of flotillin-1 and caveolin-1 during the invasion of S. agalactiae strain in HUVEC cells. CONCLUSIONS: The collection of our results suggests that lipid microdomain affects the interaction of S. agalactiae type III belonging to the hypervirulent ST-17 with HUVEC cells through PI3K/Akt signaling pathway.


Commentary: The double responsibility of the thoracic surgeon at the time of the pandemic: a perspective from the North of Italy


title: The elusive function of the hepatitis C virus p7 protein

text: Abstract Hepatitis C virus (HCV) is a major global health burden with 2–3% of the world׳s population being chronically infected. Persistent infection can lead to cirrhosis and hepatocellular carcinoma. Recently available treatment options show enhanced efficacy of virus clearance, but are associated with resistance and significant side effects. This warrants further research into the basic understanding of viral proteins and their pathophysiology. The p7 protein of HCV is an integral membrane protein that forms an ion-channel. The role of p7 in the HCV life cycle is presently uncertain, but most of the research performed to date highlights its role in the virus assembly process. The aim of this review is to provide an overview of the literature investigating p7, its structural and functional details, and to summarize the developments to date regarding potential anti-p7 compounds. A better understanding of this protein may lead to development of a new and effective therapy.


docid: zbzrxuoh

title: CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia at admission in Wuhan, China

text: Abstract Purpose Aimed to characterize the CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia. Methods Asymptomatic cases with COVID-19 pneumonia confirmed by SARS-COV-2 nucleic acid testing in Renmin Hospital of Wuhan University were retrospectively enrolled. The characteristics of CT imaging and clinical feature were collected and analyzed. Results 58 asymptomatic cases with COVID-19 pneumonia admitted to our hospital between Jan 1, 2020 and Feb 23, 2020 were enrolled. All patients had history of exposure to SARS-CoV-2. On admission, patients had no symptoms and laboratory findings were normal. The predominant feature of CT findings in this cohort was ground glass opacity (GGO) (55, 94.8%) with peripheral (44, 75.9%) distribution, unilateral location (34, 58.6%) and mostly involving one or two lobes (38, 65.5%), often accompanied by characteristic signs. After short-term follow-up, 16 patients (27.6%) presented symptoms with lower lymphocyte count and higher CRP, mainly including fever, cough and fatigue. The evolution of lesions on CT imaging were observed in 10 patients (17.2%). The average days of hospitalization was19.80±10.82 days, and was significantly longer in progression patients (28.60±7.55 day). Conclusion CT imaging of asymptomatic cases with COVID-19 pneumonia has definite characteristics. Since asymptomatic infections as “covert transmitter”, and some patients can progress rapidly in the short term. It is essential to pay attention to the surveillance of asymptomatic patients with COVID-19. CT scan has great value in screening and detecting patients with COVID-19 pneumonia, especially in the highly suspicious, asymptomatic cases with negative nucleic acid testing.


Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI)-Associated Interstitial Lung Disease During the COVID-19 Pandemic


docid: tymdjrav

title: Intestinal protection against challenge with transmissible gastroenteritis virus of pigs immune after infection with the porcine respiratory coronavirus

text: Abstract An infection of pigs with the porcine respiratory coronavirus (PRCV) induces antibodies which neutralize the enteropathogenic transmissible gastroenteritis virus (TGEV) and PRCV to the same titre. In the present study, 10-week-old seronegative pigs (n = 8), pigs immune following TGEV inoculation (n = 4) or pigs immune following aerosol (n = 8) or intragastric inoculation (n = 4) with PRCV were challenged with TGEV. Whereas TGEV-immune pigs were completely protected against challenge, all PRCV-immune pigs showed serological evidence of TGEV replication. Nevertheless, the aerosol or intragastric inoculation with PRCV primed the humoral immune system against TGEV and the TGEV challenge induced a secondary antibody response in most PRCV-immune pigs. Furthermore, all PRCV-immune pigs showed a decrease in the duration of the excretion of infectious TGEV (0–4 days) in comparison with the duration of the virus excretion by seronegative pigs (5–6 days).


Urgent Call for Research on Middle East Respiratory Syndrome (MERS) in Korea


title: Influenza vaccination among Saudi Hajj pilgrims: Revealing the uptake and vaccination barriers

text: BACKGROUND: Hajj is the world’s largest annual mass gathering that attracts two to three million Muslims from around the globe to a religious assemblage in Makkah, Saudi Arabia. The risk of acquisition and transmission of influenza among Hajj pilgrims is high. Therefore, influenza vaccination is recommended, and was monitored frequently among pilgrims from different countries. However, the vaccination uptake among Saudi pilgrims has not been assessed in recent years. OBJECTIVE: This analysis aims to evaluate influenza vaccine uptake among Saudi Hajj pilgrims, and identify the key barriers to vaccination. METHOD: Data on influenza vaccination were obtained from Saudi pilgrims who took part in a large trial during the Hajj of 2013, 2014 and 2015. Pilgrims were met and recruited in Mina, Makkah during the peak period of Hajj and were asked to complete a baseline questionnaire that recorded their influenza vaccination history, including reason(s) for non-receipt of vaccine. RESULTS: A total of 6974 Saudi pilgrims aged between 18 and 95 (median 34) years were recruited; male to female ratio was 1:1.2. Of the total, 90.8% declared their influenza vaccination history, 51.3% of them reported receiving influenza vaccine before travel to Hajj. The vaccination rates for the years 2013, 2014 and 2015 were 21.4%, 48.2% and 58.1%, respectively (P < 0.001). Of 1,269 pilgrims who were at higher risk of severe disease, 54.5% received the vaccine. Lack of awareness (47.5%), reliance on natural immunity (15.8%) and being busy (15.5%) were the main reasons for non-receipt. CONCLUSION: These data from a convenience sample indicate that influenza vaccine uptake among Saudi Hajj pilgrims is increasing over years but still needs further improvement. Lack of awareness and misperceptions are the main barriers. Education of Saudi pilgrims and health professionals is required to raise awareness about influenza vaccination. Further studies are needed to understand pilgrims’ misperceptions.


title: The antiviral effect of interferon-beta against SARS-Coronavirus is not mediated by MxA protein

text: Abstract Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus termed SARS-CoV. No antiviral treatment has been established so far. Interferons are cytokines which induce the synthesis of several antivirally active proteins in the cell. In this study, we demonstrated that multiplication of SARS-CoV in cell culture can be strongly inhibited by pretreatment with interferon-beta. Interferon-alpha and interferon-gamma, by contrast, were less effective. The human MxA protein is one of the most prominent proteins induced by interferon-beta. Nevertheless, no interference with SARS-CoV replication was observed in Vero cells stably expressing MxA. Therefore, other interferon-induced proteins must be responsible for the strong inhibitory effect of interferon-beta against SARS-CoV.


title: Refinement and 3D‐QSAR Studies of Inhibitors of Cyclophilin A Containing Amide Linker

text: Cyclophilin A (CypA) is a ubiquitous cellular enzyme playing essential role in many biological processes, and the discovery of CypA inhibitor is now of special interest in the treatment of immunological disorders. In this work, molecular modeling studies were performed to develop a predictive Common Pharmacophore Hypothesis (CPH) and use it for alignment in 3D‐QSAR studies using CoMFA and CoMSIA. A total of 30 compounds containing an amide fragment as the key linker, consisting of 17 of our previously discovered CypA inhibitors and 13 other inhibitors reported in the literature, were selected for pharmacophore refinement and 3D‐QSAR studies. The best pharmacophore hypothesis AADR, which had two hydrogen bond acceptors, a hydrogen bond donor, and an aromatic ring, was obtained and used for the alignment of molecules in CoMFA and CoMSIA model development. The models showed a good r (2) value of 0.992 and 0.949 for CoMFA and CoMSIA, respectively. The contour maps of the models were analyzed to give structural insight for activity improvement of future novel CypA inhibitors. The CPH can also provide a powerful template for virtual screening and design of new CypA inhibitors.


title: Synergistic Inhibitor Binding to the Papain-Like Protease of Human SARS Coronavirus – Mechanistic and Inhibitor Design Implications

text: We have previously developed two potent chemical classes that inhibit the essential papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus (SARS-CoV). In this study, we applied a novel approach to identify small fragments that act synergistically with these inhibitors. A fragment library was screened in combination with four previously developed lead inhibitors by fluorescence-based enzymatic assays. Several fragment compounds synergistically enhanced the inhibitory activity of the lead inhibitors by approximately an order of magnitude. Surface plasmon resonance (SPR) measurements showed that three fragments bind specifically to the PLpro enzyme. Mode of inhibition, computational solvent mapping, and molecular docking studies suggest that these fragments bind adjacent to the binding site of the lead inhibitors and further stabilize the inhibitor-bound state. We propose potential next generation compounds based upon a computational, fragment-merging approach. This approach provides an alternative strategy for lead optimization in cases where direct co-crystallization is difficult.


title: Oral vesiculobullous lesions associated with SARS‐CoV‐2 infection

text: The coronavirus pandemic that began in China at the end of last year, claimed its first confirmed death in Spain at the end of January 2020, where to date, 200,000 infections and 20,852 deaths have been recorded. In addition to the manifestations of SARS-CoV-2 infection described in the literature (fever, dry cough, diarrhea, and respiratory involvement) recently, skin exanthematic lesions have been described. We present three cases (two suspected and one confirmed) of patients presenting ulcers in the oral cavity. Oral manifestations developed during the lock-down period between the last week of March and the first week of April 2020, and consisted of pain, desquamative gingivitis, ulcers and blisters. To the best of our knowledge, this is the first case report describing of a COVID-19 patient with oral manifestations. Intraoral examinations should be carried out in patients affected by SARS-CoV-2, always when having the recommended protection measures available to a better understanding of the disease.


title: Exploiting lectin affinity chromatography in clinical diagnosis

text: Abstract Lectin affinity chromatography (LAC) offers a tool that aids purification of cell surface glycoconjugates in sufficient quantities so that studies addressing their structural elucidation could be carried out. It has several advantages over the conventional biochemical methods, such as immunoprecipitation and/or immunoaffinity chromatography, used for the purification of various glycoconjugates. Serial LAC (SLAC) not only helps establish the identity of a glycoprotein or allows purification of a glycoprotein to homogeneity from among a mixture of glycoproteins, but it also successfully resolves the microheterogeneity in these glycoproteins, which is an otherwise impracticable problem to address. Specific cases of the altered expression and maintenance of microheterogeneity of some of the glycoproteins in pathological conditions vis a vis during normal biology are presented. The application of LAC in (i) itself, (ii) a serial fashion, and (iii) conjunction with other techniques such as two-dimensional electrophoresis, capillary electrophoresis, mass spectrometry, etc. in the diagnosis of certain pathological conditions, and the possibility of using this knowledge in designing treatments for various diseases, is discussed.


docid: otxxbyfw

title: Information technology and patient safety in nursing practice: an international perspective

text: Abstract When people become patients, they place their trust in their health care providers. As providers assume responsibility for their diagnosis and treatment, patients have a right to expect that this will include responsibility for their safety during all aspects of care. However, increasing epidemiological data make it clear that patient safety is a global problem. Improved nursing care may prevent many adverse events, and nursing must take a stronger leadership role in this area. Although errors are almost inevitable, safety can be improved, and health care institutions are increasingly making safety a top priority. Information technology provides safety benefits by enhancing communication and delivering decision-support; its use will likely be a cornerstone for improving safety. This paper will discuss the status of patient safety from an international viewpoint, provide case studies from different countries, and discuss information technology solutions from a nursing perspective.


title: Availability of Personal Protective Equipment (PPE) Among US and Pakistani Doctors in COVID-19 Pandemic

text: Background The coronavirus disease (COVID-19) pandemic has put an excessive strain on healthcare systems across the globe, causing a shortage of personal protective equipment (PPE). PPE is a precious commodity for health personnel to protect them against infections. We investigated the availability of PPE among doctors in the United States (US) and Pakistan. Methods A cross-sectional study, including doctors from the US and Pakistan, was carried out from April 8 to May 5, 2020. An online self-administered questionnaire was distributed to doctors working in hospitals in the US and Pakistan after a small pilot study. All analysis was done using Statistical Package for Social Science (SPSS) version 23.0 (IBM Corp., Armonk, NY). Results After informed consent, 574 doctors (60.6% from Pakistan and 39.4% from the US) were included in the analysis. The majority of the participants were females (53.3%), and the mean age of the participants was 35.3 ± 10.3 years. Most doctors (47.7%) were from medicine and allied fields. Among the participants, 87.6% of doctors from the US reported having access to masks/N95 respirators, 79.6% to gloves, 77.9% to face-shields or goggles, and 50.4% to full-suit/gown. Whereas, doctors in Pakistan reported to have poor availability of PPE with only 37.4% having access to masks/N95 respirator, 34.5% to gloves, 13.8% to face-shields or goggles, and 12.9% to full-suit/gown. The reuse of PPE was reported by 80.5% and 60.3% physicians from the US and Pakistan, respectively. More doctors from Pakistan (50.6%) reported that they had been forced to work without PPE compared to doctors in the US (7.1%). Conclusion There is a lack of different forms of PPE in the US and Pakistan. Doctors from both countries reported that they had been forced to work without PPE. Compared to the US, more doctors from Pakistan reported having faced discrimination in receiving PPE.


title: Middle East respiratory syndrome coronavirus infection in non-camelid domestic mammals

text: Dromedary camels are natural host of the Middle East respiratory syndrome coronavirus (MERS-CoV). However, there are limited studies of MERS-CoV infection of other domestic mammals exposed to infected dromedaries. We expanded our surveillance among camels in Egypt, Tunisia, and Senegal to include other domestic mammalian species in contact with infected camels. A total of 820 sera and 823 nasal swabs from cattle, sheep, goats, donkeys, buffaloes, mules, and horses were collected. Swabs were tested using RT-PCR and virus RNA-positive samples were genetically sequenced and phylogenetically analysed. Sera were screened using virus microneutralization tests and positive sera (where available) were confirmed using plaque reduction neutralization tests (PRNT). We detected 90% PRNT confirmed MERS-CoV antibody in 35 (55.6%) of 63 sera from sheep collected from Senegal, two sheep (1.8%) of 114 in Tunisia and a goat (0.9%) of 107 in Egypt, with titres ranging from 1:80 to ≥1:320. We detected MERS-CoV RNA in swabs from three sheep (1.2%) of 254 and five goats (4.1%) of 121 from Egypt and Senegal, as well as one cow (1.9%) of 53 and three donkeys (7.1%) of 42 from Egypt. Partial sequences of the RT-PCR amplicons confirmed specificity of the results. This study showed that domestic livestock in contact with MERS-CoV infected camels may be at risk of infection. We recommend expanding current MERS-CoV surveillance in animals to include other livestock in close contact with dromedary camels. The segregation of camels from other livestock in farms and live animal markets may need to be considered.


Middle East respiratory syndrome coronavirus (MERS-CoV): threats, gaps and containment strategies


Epidemiologic characteristic of human Middle East respiratory syndrome in Saudi Arabia, 2015–2017


title: Interventions as experiments: Connecting the dots in forecasting and overcoming pandemics, global warming, corruption, civil rights violations, misogyny, income inequality, and guns

text: This essay applies the “ultimate broadening of the concept of marketing” for designing and implementing interventions in public laws and policy, national and local regulations, and everyday lives of individuals. The ultimate broadening of the concept of marketing: Marketing is any activity, message, emotion, or behavior by someone, firm, organization, government, community, or brand executed consciously or nonconsciously that may stimulate an observable or non-observable activity, emotion, attitude, belief, or thought by someone else, group, organization, firm or community. The broadening definition applies to the current interventions by national and state/provincial governments as well as healthcare facilities, medical science facilities, firms, and individuals to mitigate and eliminate the impact of the COVID-19 pandemic. Framing interventions as experiments is helpful in improving the quality of their designs, implementing them successfully, and validly interpreting their effectiveness. In January and February 2020, a few nations were exemplars for accurately forecasting the coming disaster of COVID-19 as a cause of illness and death and in designing/implementing effective mitigating strategies: Denmark, Finland, Republic of Korea, New Zealand, Norway, and Vietnam. While the COVID-19 prevention intervention tests now being run for several promising vaccines are true experiments, the researchers analyzing the data from these interventions may need prompting to examine the efficacy of each vaccine tested by modeling demographic subgroups for the members in the treatment and placebo groups in the randomized control trials.


docid: doizzbir

title: Surveillance for respiratory infectious diseases caused by 6 common viruses in a recruit training site in the Northern region of China

text: BACKGROUND: Recruit training sites are places with a high incidence of respiratory infectious diseases. Effective surveillance for acute respiratory infectious diseases in a recruit training site is an important way to prevent disease outbreaks. METHODS: Eight hundred recruits (722 males and 78 females) enlisted in autumn 2015 received a background survey within 24 h of settlement at the recruit training site, including their general personal information, vaccination history, mental status and clinical symptoms. Then, nasopharyngeal swabs of these recruits were collected to detect common respiratory pathogens [influenza virus type A, influenza virus type B, adenovirus (Adv), human respiratory syncytial virus, human bocavirus and human metapneumovirus] by PCR. In addition, fasting venous blood was collected in the morning for adenovirus IgG antibody detection. During the three months of training, the recruits were monitored for symptoms of respiratory infection, and nasopharyngeal swabs were collected from those with an axillary temperature ≥38 °C and other respiratory symptoms within 4 h of symptom onset. Samples were further examined by PCR. RESULTS: Among the 795 effective nasopharyngeal swab samples collected during survey, two cases of group C type 1 adenovirus were identified by PCR. During the 3 months of training, fever and respiratory symptoms occurred in 39 recruits (incidence rate of 4.9%) and 5 cases of adenovirus were detected (positive rate of 12.8%). Genotyping showed 3 cases of type 4 adenovirus and 2 of type 3 adenovirus. No type 7, 14 or 55 adenovirus was detected. The Adv-IgG positive rate of recruits was 48.2%. Among the 5 Adv positive cases with fever and respiratory symptoms, 4 were Adv-IgG positive. CONCLUSION: The pathogen carrier rate in recruits was low, and only group C adenovirus, which causes mild infection in humans, was detected. No respiratory outbreak was observed at the recruit training site, and sporadic cases were mainly caused by type 3 and type 4 adenoviruses.


title: Vaccines for the twenty-first century society

text: Vaccines have been one of the major revolutions in the history of mankind and, during the twentieth century, they eliminated most of the childhood diseases that used to cause millions of deaths. In the twenty-first century, vaccines will also play a major part in safeguarding people's health. Supported by the innovations derived from new technologies, vaccines will address the new needs of a twenty-first century society characterized by increased life expectancy, emerging infections and poverty in low-income countries.


title: Highly conserved epitopes of DENV structural and non-structural proteins: Candidates for universal vaccine targets

text: Abstract Dengue is a severe emerging arthropod borne viral disease occurring globally. Around two fifths of the world's population, or up to 3.9 billion people, are at a risk of dengue infection. Infection induces a life-long protective immunity to the homologous serotype but confers only partial and transient protection against subsequent infection caused by other serotypes. Thus, there is a need for a vaccine which is capable of providing a life- long protection against all the serotypes of dengue virus. In our study, comparative genomics of Dengue virus (DENV) was conducted to explore potential candidates for novel vaccine targets. From our analysis we successfully found 100% conserved epitopes in Envelope protein (RCPTQGE); NS3 (SAAQRRGR, PGTSGSPI); NS4A (QRTPQDNQL); NS4B (LQAKATREAQKRA) and NS5 proteins (QRGSGQV) in all DENV serotypes. Some serotype specific conserved motifs were also found in NS1, NS5, Capsid, PrM and Envelope proteins. Using comparative genomics and immunoinformatics approach, we could find conserved epitopes which can be explored as peptide vaccine candidates to combat dengue worldwide. Serotype specific epitopes can also be exploited for rapid diagnostics. All ten proteins are explored to find the conserved epitopes in DENV serotypes, thus making it the most extensively studied viral genome so far.


At the US Epicenter of the COVID-19 Pandemic, an Orthopedic Residency Program Reorganizes


title: Cerebrovascular Disease in Patients with COVID-19: A Review of the Literature and Case Series

text: COVID-19 has been associated with a hypercoagulable state causing cardiovascular and neurovascular complications. To further characterize cerebrovascular disease (CVD) in COVID-19, we review the current literature of published cases and additionally report the clinical presentation, laboratory and diagnostic testing results of 12 cases with COVID-19 infection and concurrent CVD from two academic medical centers in Houston, TX, USA, between March 1 and May 10, 2020. To date, there are 12 case studies reporting 47 cases of CVD in COVID-19. However, only 4 small case series have described the clinical and laboratory findings in patients with COVID-19 and concurrent stroke. Viral neurotropism, endothelial dysfunction, coagulopathy and inflammation are plausible proposed mechanisms of CVD in COVID-19 patients. In our case series of 12 patients, 10 patients had an ischemic stroke, of which 1 suffered hemorrhagic transformation and two had intracerebral hemorrhage. Etiology was determined to be embolic without a clear cause identified in 6 ischemic stroke patients, while the remaining had an identifiable source of stroke. The majority of the patients had elevated inflammatory markers such as D-dimer and interleukin-6. In patients with embolic stroke of unclear etiology, COVID-19 may have played a direct or indirect role in the processes that eventually led to the strokes while in the remaining cases, it is unclear if infection contributed partially or was an incidental finding.


title: Patterns of mortality during pandemic: An example of Spanish flu pandemic of 1918

text: Now the attention of the whole world is focused on the developing pandemic of the coronavirus infection COVID-19. This article discusses mortality patterns of the deadliest epidemic in the last 120 years – the Spanish flu pandemic of 1918. Statistical sources from Italy and the USA, published shortly after the pandemic, were analyzed. The analysis was carried out for mortality from all causes, since in this case inaccuracies associated with establishing the causes of death are minimized. Despite the fact that the first cases of the Spanish flu appeared in the United States as early as March 1918, this first wave of epidemic practically did not affect the total mortality rate. The main peak of mortality in 1918 occurred in October 1918 both in the USA and Italy, with a gradual decrease in mortality over several months. Analysis of age-specific mortality demonstrates a significant increase in mortality at middle ages (20–50 years) in 1918 compared with 1917. Analysis of mortality trends using the method of latent variables shows a significant increase in the background mortality factor in 1918, which turned out to be higher for Italy than the mortality losses during the Second World War. The Spanish flu pandemic differs from the current coronavirus pandemic, because of significant increase in mortality of middle-aged people, while the COVID-19 pandemic causes a more marked increase in mortality among the elderly. With this, the COVID-19 pandemic is more like the recent flu epidemics than the earlier Spanish flu pandemic.


title: Diagnostic test for etiologic agents of community-acquired pneumonia

text: Diagnostic tests for the detection of the etiologic agent of pneumonia are neither recommended nor done for most outpatients with CAP (Table 4).Most of these patients have no clear diagnosis but seem to do well with empiric antibiotic treatment, which often costs less than the diagnostic tests. For hospitalized patients, a pre-treatment blood culture and an expectorated sputum gram stain and culture should be done. Testing for Legionella spp is appropriate in hospitalized patients, especially those who are seriously ill. New tests that merit use in selected patients are the urinary antigen assay for S pneumoniae and the PCR test for L pneumophila. Anticipated developments in the near future are PCR tests for detection of C pneumoniae and M pneumoniae.


title: Anticancer drugs and COVID-19 antiviral treatments in cancer patients: what can we safely use?

text: • More safety data is needed to treat COVID-19 symptomatic patients with anticancer drugs known to increase infections. • We summarized immunosuppressing anticancer drugs; other drugs were studied for drug-drug interactions with antiviral medicines. • A ready-to-use table synthetize these pharmacokinetic and pharmacodynamic interactions between antiviral and anticancer drugs.


The load and capacity model of healthcare delivery: considerations for the crisis management of the COVID-19 pandemic


title: Neonatal bronchial hyperresponsiveness precedes acute severe viral bronchiolitis in infants

text: Background Respiratory syncytial virus and other respiratory tract viruses lead to common colds in most infants, whereas a minority develop acute severe bronchiolitis often requiring hospitalization. We hypothesized that such an excessive response to respiratory tract viral infection is caused by host factors reflected in pre-existing increased bronchial responsiveness. Objective We sought to compare bronchial responsiveness and lung function in 1-month-old neonates who later develop acute severe bronchiolitis with those who do not. Methods We measured infant lung function (n = 402) and bronchial responsiveness to methacholine (n = 363) using the raised-volume rapid thoracoabdominal compression technique before any respiratory symptoms in 1-month-old neonates from the Copenhagen Prospective Study of Asthma in Childhood birth cohort born to mothers with asthma. The children were prospectively monitored for respiratory symptoms and given a diagnosis of acute severe bronchiolitis according to a fixed algorithm. Results Thirty-four (8.5%) infants had acute severe bronchiolitis before 2 years of age, 21 (62%) were hospitalized, and 23 (67%) of the cases were associated with respiratory syncytial virus. Children who later had acute severe bronchiolitis irrespective of viral species had a 2.5-fold increased responsiveness to methacholine (provocative dose of methacholine producing a 15% decrease in transcutaneous oxygen pressure [PD15]) at age 1 month compared with control subjects (median PD15 in cases vs control subjects, 0.13 vs 0.33 μmol; P = .01), whereas differences in baseline airflow were not significant for forced expiratory volume at 0.5 seconds (mean z score for cases vs control subjects, −0.18 vs −0.01; P = .36) and forced expiratory flow at 50% of forced vital capacity (mean z score for cases vs control subjects, −0.37 vs −0.09; P = .13). Conclusion Bronchial hyperresponsiveness in at-risk neonates precedes acute severe bronchiolitis in response to infections with respiratory tract virus.


title: Development of pooled testing system for porcine epidemic diarrhoea using real-time fluorescent reverse-transcription loop-mediated isothermal amplification assay

text: BACKGROUND: Porcine epidemic diarrhoea (PED) is an emerging disease in pigs that causes massive economic losses in the swine industry, with high mortality in suckling piglets. Early identification of PED virus (PEDV)-infected herd through surveillance or monitoring strategies is necessary for mass control of PED. However, a common working diagnosis system involves identifying PEDV-infected animals individually, which is a costly and time-consuming approach. Given the above information, the thrusts of this study were to develop a real-time fluorescent reverse transcription loop-mediated isothermal amplification (RtF-RT-LAMP) assay and establish a pooled testing system using faecal sample to identify PEDV-infected herd. RESULTS: In this study, we developed an accurate, rapid, cost-effective, and simple RtF- RT-LAMP assay for detecting the PEDV genome targeting M gene. The pooled testing system using the RtF-RT-LAMP assay was optimized such that a pool of at least 15 individual faecal samples could be analysed. CONCLUSIONS: The developed RtF-RT-LAMP assay in our study could support the design and implementation of large-scaled epidemiological surveys as well as active surveillance and monitoring programs for effective control of PED. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1498-9) contains supplementary material, which is available to authorized users.


title: Vaccine confidence in the time of COVID-19

text: In the early months of the COVID-19 epidemic, some have wondered if the force of this global experience will solve the problem of vaccine refusal that has vexed and preoccupied the global public health community for the last several decades. Drawing on historical and epidemiological analyses, we critique contemporary approaches to reducing vaccine hesitancy and articulate our notion of vaccine confidence as an expanded way of conceptualizing the problem and how to respond to it. Intervening on the rush of vaccine optimism we see pervading present discourse around the COVID-19 epidemic, we call for a re-imagination of the culture of public health and the meaning of vaccine safety regulations. Public confidence in vaccination programs depends on the work they do for the community—social, political, and moral as well as biological. The concept of public health and its programs must be broader than the delivery of the vaccine technology itself. The narrative work and policy actions entailed in actualizing such changes will, we expect, be essential in achieving a true vaccine confidence, however the public reacts to the specific vaccine that may be developed for COVID-19.


docid: shlhreve

title: Global research trends of World Health Organization’s top eight emerging pathogens

text: BACKGROUND: On December 8(th), 2015, World Health Organization published a priority list of eight pathogens expected to cause severe outbreaks in the near future. To better understand global research trends and characteristics of publications on these emerging pathogens, we carried out this bibliometric study hoping to contribute to global awareness and preparedness toward this topic. METHOD: Scopus database was searched for the following pathogens/infectious diseases: Ebola, Marburg, Lassa, Rift valley, Crimean-Congo, Nipah, Middle Eastern Respiratory Syndrome (MERS), and Severe Respiratory Acute Syndrome (SARS). Retrieved articles were analyzed to obtain standard bibliometric indicators. RESULTS: A total of 8619 journal articles were retrieved. Authors from 154 different countries contributed to publishing these articles. Two peaks of publications, an early one for SARS and a late one for Ebola, were observed. Retrieved articles received a total of 221,606 citations with a mean ± standard deviation of 25.7 ± 65.4 citations per article and an h-index of 173. International collaboration was as high as 86.9%. The Centers for Disease Control and Prevention had the highest share (344; 5.0%) followed by the University of Hong Kong with 305 (4.5%). The top leading journal was Journal of Virology with 572 (6.6%) articles while Feldmann, Heinz R. was the most productive researcher with 197 (2.3%) articles. China ranked first on SARS, Turkey ranked first on Crimean-Congo fever, while the United States of America ranked first on the remaining six diseases. Of retrieved articles, 472 (5.5%) were on vaccine – related research with Ebola vaccine being most studied. CONCLUSION: Number of publications on studied pathogens showed sudden dramatic rise in the past two decades representing severe global outbreaks. Contribution of a large number of different countries and the relatively high h-index are indicative of how international collaboration can create common health agenda among distant different countries.


title: Highly multiplexed oligonucleotide probe-ligation testing enables efficient extraction-free SARS-CoV-2 detection and viral genotyping

text: The emergence of SARS-CoV-2 has caused the current COVID-19 pandemic with catastrophic societal impact. Because many individuals shed virus for days before symptom onset, and many show mild or no symptoms, an emergent and unprecedented need exists for development and deployment of sensitive and high throughput molecular diagnostic tests. RNA-mediated oligonucleotide Annealing Selection and Ligation with next generation DNA sequencing (RASL-seq) is a highly multiplexed technology for targeted analysis of polyadenylated mRNA, which incorporates sample barcoding for massively parallel analyses. Here we present a more generalized method, capture RASL-seq (“cRASL-seq”), which enables analysis of any targeted pathogen- (and/or host-) associated RNA molecules. cRASL-seq enables highly sensitive (down to ~1–100 pfu/ml or cfu/ml) and highly multiplexed (up to ~10,000 target sequences) detection of pathogens. Importantly, cRASL-seq analysis of COVID-19 patient nasopharyngeal (NP) swab specimens does not involve nucleic acid extraction or reverse transcription, steps that have caused testing bottlenecks associated with other assays. Our simplified workflow additionally enables the direct and efficient genotyping of selected, informative SARS-CoV-2 polymorphisms across the entire genome, which can be used for enhanced characterization of transmission chains at population scale and detection of viral clades with higher or lower virulence. Given its extremely low per-sample cost, simple and automatable protocol and analytics, probe panel modularity, and massive scalability, we propose that cRASL-seq testing is a powerful new surveillance technology with the potential to help mitigate the current pandemic and prevent similar public health crises.


docid: woyysdvo

title: Outpatient treatment of COVID-19 with steroids in the phase of mild pneumonia without the need for admission as an opportunity to modify the course of the disease: A structured summary of a randomised controlled trial

text: OBJECTIVES: The aim of this study is to explore the effectiveness and safety of oral corticosteroids (prednisone) in the treatment of early stage SARS-Cov-2 pneumonia in patients who do not yet meet hospital admission criteria. TRIAL DESIGN: Randomized clinical trial, controlled, open, parallel group, to evaluate the effectiveness of steroids in adult patients with confirmed COVID-19, with incipient pulmonary involvement, without hospital admission criteria. Patients will be stratified by the presence or not of radiological data on pneumonia. PARTICIPANTS: We will include patients with early stage SARS-Cov-2 pneumonia who do not meet hospital admission criteria from the reference hospital, the Hospital Universitario de Burgos, in the region of Castilla y León, Spain. Patients will be followed-up by specialist physicians and Primary Health Care professionals. Inclusion criteria: - Men and women. - Age between 18 and 75 years old. - Diagnosed SARS-CoV-2 infection, by PCR and/or IgM+ antibody test and/or antigen test. - Clinical diagnosis of lung involvement: (respiratory symptoms +/- pathological auscultation +/- O2 desaturation) - Chest X-ray with mild-moderate alterations or normal. - Patients who give their verbal informed consent in front of witnesses, which will be reflected in the patients’ medical records. Exclusion criteria: - Oxygen desaturation below 93% or P0(2) < 62. - Moderate-severe dyspnea or significant respiratory or general deterioration that makes admission advisable. - Chest X-ray with multifocal infiltrates. - Insulin-dependent diabetes with poor control or glycaemia in the emergency room test greater than 300 mg/ml (fasting or not). - Other significant comorbidities: Severe renal failure (creatinine clearance < 30 mL/min); cirrhosis or chronic liver disease, poorly controlled hypertension. - Heart rhythm disturbances (including prolonged QT). - Severe immunosuppression (HIV infection, long-term use of immunosuppressive agents); cancer. - Pregnant or breast-feeding women. - Patients under use of glucocorticoids for other diseases. - History of allergy or intolerance to any of the drugs in the study (prednisone, azithromycin or hydroxychloroquine). - Patients who took one or more of the study drugs in the 7 days prior to study inclusion. - Patients taking non-suppressible drugs with risk of QT prolongation or significant interactions. - Patients unwilling or unable to participate until study completion. - Participation in another study. INTERVENTION AND COMPARATOR: Eligible patients will be randomized to receive standard outpatient treatment only (group 1) or standard outpatient treatment plus prednisone (group 2). - Group 1: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days. - Group 2: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days + prednisone 60 mg / 24 h for 3 days, 30 mg / 24 h for 3 days and 15 mg / 24 h for 3 days. MAIN OUTCOMES: If the patient requires ambulatory observation, according to the protocol established in this respect in the Emergency Department, meets all the criteria for inclusion and none for exclusion, data will be taken by the person responsible on the data collection sheet. The main result is admission after 30 days. Secondary outcomes are 30-day ICU admission and hospital stay. The safety variable will be the occurrence of clinical symptoms or delirium related to the steroids. Also, the possible decompensations of diabetes will be measured. All tests will be on an intention-to-treat basis. RANDOMISATION: Treatment will be assigned according to stratified randomization by the presence or absence of radiological data of lung involvement (previously performed by random sequence 1:1 generated with Epidat and kept hidden by opaque, sealed envelopes, which will only be opened after inclusion and basal measurement). BLINDING (MASKING): Participants, caregivers and personnel responsible for outcomes measurement will not be blinded to group assignment, once the patient is included and the basal measurement performed, as per protocol design. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The percentage of patients with incipient lung involvement is unknown, but given that pulmonary involvement already exists it is estimated to be around 20%. We consider that the intervention could reduce this percentage to 5%, so the necessary sample size would be 200 subjects (100 per group), with a power of 80% and an estimated loss percentage of 10%. TRIAL STATUS: The protocol with code TAC-COVID-19, version 2.0 on date: April 16, 2020 is approved by the Spanish Drug Agency (AEMPS) and the local Ethics Committee. The trial is in the recruitment phase. Recruitment began 19 April, 2020 and is anticipated to be complete by April 2021. TRIAL REGISTRATION: The trial was registered under the title “OUTPATIENT TREATMENT OF EARLY PULMONARY COVID19 WITH CORTICOSTEROIDS AS AN OPPORTUNITY TO MODIFY THE COURSE OF THE DISEASE” with EudraCT number 2020-001622-64, registered on 3 April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


title: Viral Etiology of Acute Respiratory Infection in Gansu Province, China, 2011

text: BACKGROUND: Acute respiratory infections (ARIs) are the leading cause of children and their leading killer. ARIs are responsible for at least six percent of the world's disability and death. Viruses are one of the most common agents causing ARIs. Few studies on the viral etiology and clinical characteristics of ARIs have been performed in the northwest region of China, including Gansu Province. METHODS: Clinical and demographic information and throat swabs were collected from 279 patients from January 1st to December 30st, 2011. Multiplex RT-PCR was performed to detect 16 respiratory viral pathogens. RESULTS: 279 patients were admitted for ARIs. The patients aged from 1 month to 12 years, with the median age of 2 years. Of which, 105 (37.6%) were positive for at least one pathogen. A total of 136 respiratory viral pathogens were identified from the 105 patients. Respiratory syncytial virus (RSV) was the most frequently detected pathogen (26.5%, 36/136), followed by parainfluenza virus (PIV) 1–3 (22.1%, 30/136), human rhinovirus (HRV) (21.3%, 29/136), human coronavirus (CoV) (10.3%, 14/136) and human adenovirus (HAdV) (9.6%, 13/136). Influenza A (Flu A), human metapneumovirus (hMPV) and human bocavirus (BoCA) were found 4.4%, 3.7% and 2.2%, respectively. Influenza B (Flu B) and seasonal influenza A H1N1(sH1N1) were not detected. Single-infections were detected in 30.5% (85/279) of cases. RSV was the most common pathogens in patients under 1 year and showed seasonal variation with peaks during winter and spring. CONCLUSIONS: This paper presents data on the epidemiology of viral pathogens associated with ARIs among children in Gansu Province, China. RSV is most frequently detected in our study. The findings could serve as a reference for local CDC in drawing up further plans to prevent and control ARIs.


title: Emergence of Kawasaki disease related to SARS-CoV-2 infection in an epicentre of the French COVID-19 epidemic: a time-series analysis

text: BACKGROUND: Kawasaki disease is an acute febrile systemic childhood vasculitis, which is suspected to be triggered by respiratory viral infections. We aimed to examine whether the ongoing COVID-19 epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with an increase in the incidence of Kawasaki disease. METHODS: We did a quasi-experimental interrupted time series analysis over the past 15 years in a tertiary paediatric centre in the Paris region, a French epicentre of the COVID-19 outbreak. The main outcome was the number of Kawasaki disease cases over time, estimated by quasi-Poisson regression. In the same centre, we recorded the number of hospital admissions from the emergency department (2005–2020) and the results of nasopharyngeal multiplex PCR to identify respiratory pathogens (2017–2020). These data were compared with daily hospital admissions due to confirmed COVID-19 in the same region, recorded by Public Health France. FINDINGS: Between Dec 1, 2005, and May 20, 2020, we included 230 patients with Kawasaki disease. The median number of Kawasaki disease hospitalisations estimated by the quasi-Poisson model was 1·2 per month (IQR 1·1–1·3). In April, 2020, we identified a rapid increase of Kawasaki disease that was related to SARS-CoV-2 (six cases per month; 497% increase [95% CI 72–1082]; p=0·0011), starting 2 weeks after the peak of the COVID-19 epidemic. SARS-CoV-2 was the only virus circulating intensely during this period, and was found in eight (80%) of ten patients with Kawasaki disease since April 15 (SARS-CoV-2-positive PCR or serology). A second peak of hospital admissions due to Kawasaki disease was observed in December, 2009 (six cases per month; 365% increase ([31–719]; p=0.0053), concomitant with the influenza A H1N1 pandemic. INTERPRETATION: Our study further suggests that viral respiratory infections, including SAR-CoV-2, could be triggers for Kawasaki disease and indicates the potential timing of an increase in incidence of the disease in COVID-19 epidemics. Health-care providers should be prepared to manage an influx of patients with severe Kawasaki disease, particularly in countries where the peak of COVID-19 has recently been reached. FUNDING: French National Research Agency.


title: COVID-19: A case series to support radiographer preliminary clinical evaluation

text: The case series provides radiographers with essential information to preliminarily evaluate chest imaging and prompt the rapid diagnosis of COVID-19. [Figure: see text]


title: Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

text: Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.


title: PCR testing for Paediatric Acute Respiratory Tract Infections

text: Summary Acute respiratory tract infection (ARI) is a frequently occurring disease in children. It is a clinical diagnosis for which no internationally accepted diagnostic test is available. The majority of ARI is viral in origin, though diagnostic tests for viruses were rarely performed in the past. In the past 2 decades, new molecular techniques have been introduced in many hospitals. They are capable of generating a high yield of viral and bacterial diagnoses, but their impact upon clinical practices is still questionable. In this paper, we discuss the difficulties of diagnosing ARI in children, the indications for conventional and new diagnostics and their implications.


title: Clinical outcomes of hemodialysis patients infected with severe acute respiratory syndrome coronavirus 2 and impact of proactive chest computed tomography scans

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that first manifested in humans in Wuhan, Hubei Province, China, in December 2019, and has subsequently spread worldwide. METHODS: We conducted a retrospective, single-center case series of the seven maintenance hemodialysis (HD) patients infected with COVID-19 at Zhongnan Hospital of Wuhan University from 13 January to 7 April 2020 and a proactive search of potential cases by chest computed tomography (CT) scans. RESULTS: Of 202 HD patients, 7 (3.5%) were diagnosed with COVID-19. Five were diagnosed by reverse transcription polymerase chain reaction (RT-PCR) because of compatible symptoms, while two were diagnosed by RT-PCR as a result of screening 197 HD patients without respiratory symptoms by chest CT. Thirteen of 197 patients had positive chest CT features and, of these, 2 (15%) were confirmed to have COVID-19. In COVID-19 patients, the most common features at admission were fatigue, fever and diarrhea [5/7 (71%) had all these]. Common laboratory features included lymphocytopenia [6/7 (86%)], elevated lactate dehydrogenase [3/4 (75%)], D-dimer [5/6 (83%)], high-sensitivity C-reactive protein [4/4 (100%)] and procalcitonin [5/5 (100%)]. Chest CT showed bilateral patchy shadows or ground-glass opacity in the lungs of all patients. Four of seven (57%) received oxygen therapy, one (14%) received noninvasive and invasive mechanical ventilation, five (71%) received antiviral and antibacterial drugs, three (43%) recieved glucocorticoid therapy and one (14%) received continuous renal replacement therapy. As the last follow-up, four of the seven patients (57%) had been discharged and three patients were dead. CONCLUSIONS: Chest CT may identify COVID-19 patients without clear symptoms, but the specificity is low. The mortality of COVID-19 patients on HD was high.


title: Gastrointestinal manifestations of HIV infection

text: Summary The harrowing picture of emaciated terminally ill AIDS patients is a reminder of our lack of understanding of immunological mechanisms that normally control opportunistic infections. Many gastrointestinal pathogens in patients with AIDS are resistant to treatment and lead inexorably to weight loss and death. Although knowledge of the pathogenesis and clinical significance of weight loss has improved considerably, this has not yet led to a sustained effort to improve nutritional status during early stages of disease.


title: The genomes of two bat species with long constant frequency echolocation calls

text: Bats can perceive the world by using a wide range of sensory systems, and some of the systems have become highly specialized, such as auditory sensory perception. Among bat species, the Old World leaf-nosed bats and horseshoe bats (rhinolophoid bats) possess the most sophisticated echolocation systems. Here, we reported the whole-genome sequencing and de novo assembles of two rhinolophoid bats – the great leaf-nosed bat (Hipposideros armiger) and the Chinese rufous horseshoe bat (Rhinolophus sinicus). Comparative genomic analyses revealed the adaptation of auditory sensory perception in the rhinolophoid bat lineages, probably resulting from the extreme selectivity used in the auditory processing by these bats. Pseudogenization of some vision-related genes in rhinolophoid bats was observed, suggesting that these genes have undergone relaxed natural selection. An extensive contraction of olfactory receptor gene repertoires was observed in the lineage leading to the common ancestor of bats. Further extensive gene contractions can be observed in the branch leading to the rhinolophoid bats. Such concordance suggested that molecular changes at one sensory gene might have direct consequences for genes controlling for other sensory modalities. To characterize the population genetic structure and patterns of evolution, we re-sequenced the genome of 20 great leaf-nosed bats from four different geographical locations of China. The result showed similar sequence diversity values and little differentiation among populations. Moreover, evidence of genetic adaptations to high altitudes in the great leaf-nosed bats was observed. Taken together, our work provided a useful resource for future research on the evolution of bats.


title: Current impact of Covid-19 pandemic on Spanish plastic surgery departments: a multi-center report

text: BACKGROUND: After its initial description in China, Covid-19 is hitting nations across the world, with Spain as the third country in number of deaths, after the USA and Italy. Similarly to what is happening in other countries, an important reduction in available operating rooms is affecting our departments. In this study, we aim to know how Covid-19 pandemic is affecting the delivery of plastic surgery services in Spain. METHODS: A questionnaire addressing some of our concerns about how the Coronavirus crisis might severelyimpact our specialty has been sent to the heads of the divisions of plastic surgery of several hospitals across Spain. RESULTS: A total of 12 plastic surgery departments from different hospitals across the country agreed to participate in the survey. Most plastic surgery teams will need to maintain 50–80% of their staff in order to be able to offer emergency and undelayable oncological procedures. The total amount of procedures currently being performed ranged from 0 to 44% of the figures before the coronavirus outbreak, except for one department, with elective surgery mainly affected. Microsurgical cases have been massively discontinued during this crisis. CONCLUSIONS: Plastic surgery delivery in the Spanish Health System is being severely impacted as a collateral damage from this pandemic. Most of the elective surgery is currently stopped. Our departments seem to be vulnerable regarding their capacity to keep offering emergency care. Level of evidence: not ratable (multi-center survey)


docid: lpcjhxvg

title: Panther Fusion® Respiratory Virus Assays for the detection of influenza and other respiratory viruses

text: Abstract Background Nucleic acid amplification tests (NAATs), such as PCR, are preferred for respiratory virus testing, due to superior diagnostic accuracy and faster turnaround time. Panther Fusion® Respiratory Assays (Fusion), which includes FluA/B/RSV (FFABR), Paraflu and AdV/hMPV/RV, offers a modular approach to syndromic testing on a fully automated platform while improving gene targets and expanding the test menu. Objectives and study design We evaluated Fusion using 275 consecutive nasopharyngeal specimens previously used in an analysis of five PCRs, as well as 225 archived specimens. Results Of the combined 500 specimens, 134 were positive for influenza A (FluA), 54 for FluB, 65 for RSV, 64 for parainfluenza (PIV), 24 for adenovirus (AdV), 21 for humanmetapneumovirus (hMPV), and 40 for rhinovirus (RV) with Fusion. Of the positive samples Fusion correlated with historical results for all but one, despite multiple freeze-thaws cycles of this collection. Fusion was positive for an additional 33 samples, including 11 FluAs, 7 RSVs, 3 PIV3s, 3 AdV, 6 hMPV and 3 RVs. These samples were retested with corresponding Prodesse (Pro) assays using quadruple sample volume. This resolver test confirmed Fusion results for an additional 4 FluAs, 4 RSVs, 1 PIV3 and 3 AdVs. The sensitivity and specificity ranges of Fusion were 99–100% and 98–100%. Limit of detection (LOD) analyses were performed on a variety of Flu isolates. The LODs ranged from 2.69 to 2.99 log copies/ml and demonstrated superior LOD as compared to previously published data for some assays or to concurrent analyses with two new commercial tests.


title: The effect of COVID-19 pandemic on seizure control and self-reported stress on epilepsy patient

text: Abstract Objectives To assess if patients with epilepsy (PWE) experienced an increase in seizure frequency and self-reported stress during the COVID-19 pandemic. Methods This is a cross-sectional study conducted in Saudi Arabia in April 2020. An electronic self-administered questionnaire was distributed to PWE via their treating neurologist. The variables included were demographic and baseline clinical characteristics (age, gender, living situation, occupational status, type of epilepsy, duration of epilepsy, number of antiepileptic medications (AEDs), presence of known psychiatric illness, and use of psychiatric medications), their seizure control in the month prior to the pandemic, perceived stress during this period of time, sleep changes, compliance changes, and change in seizure control during the pandemic. Results A total of 156 patients completed the questionnaire, with 29.5% reporting an increase in seizure frequency. Additionally, 59.4% reported an increase in self-reported stress and 71.2% experienced a significant change in their sleep during this period. Higher baseline seizure frequency, more AEDs, non-compliance, increase in self-reported stress, and sleep changes are the significant factors associated with increase in seizure frequency during the pandemic. Conclusion Identifying high-risk patients for seizure recurrence is important in order to provide them with adequate support to reduce such risk.


title: Identification of Putative ORF5 Protein of Porcine Circovirus Type 2 and Functional Analysis of GFP-Fused ORF5 Protein

text: Porcine circovirus type 2 (PCV2) is the essential infectious agent responsible for causing porcine circovirus-associated diseases in pigs. To date, eleven RNAs and five viral proteins of PCV2 have been detected. Here, we identified a novel viral gene within the PCV2 genome, termed ORF5, that exists at both the transcriptional and translational level during productive infection of PCV2 in porcine alveolar macrophages 3D4/2 (PAMs). Northern blot analysis was used to demonstrate that the ORF5 gene measures 180 bp in length and overlaps completely with ORF1 when read in the same direction. Site-directed mutagenesis was used to show that the ORF5 protein is not essential for PCV2 replication. To investigate the biological functions of the novel protein, we constructed a recombinant eukaryotic expression plasmid capable of expressing PCV2 ORF5. The results show that the GFP-tagged PCV2 ORF5 protein localizes to the endoplasmic reticulum (ER), is degraded via the proteasome, inhibits PAM growth and prolongs the S-phase of the cell cycle. Further studies show that the GFP-tagged PCV2 ORF5 protein induces ER stress and activates NF-κB, which was further confirmed by a significant upregulation in IL-6, IL-8 and COX-2 expression. In addition, five cellular proteins (GPNMB, CYP1A1, YWHAB, ZNF511 and SRSF3) were found to interact with ORF5 via yeast two-hybrid assay. These findings provide novel information on the identification and functional analysis of the PCV2 ORF5 protein and are likely to be of benefit in elucidating the molecular mechanisms of PCV2 pathogenicity. However, additional experiments are needed to validate the expression and function of the ORF5 protein during PCV2 infection in vitro before any definitive conclusion can be drawn.


title: Characterization and inhibition of norovirus proteases of genogroups I and II using a fluorescence resonance energy transfer assay

text: Abstract Noroviruses are the major cause of food- or water-borne gastroenteritis outbreaks in humans. The norovirus protease that cleaves a large viral polyprotein to nonstructural proteins is essential for virus replication and an attractive target for antiviral drug development. Noroviruses show high genetic diversity with at least five genogroups, GI–GV, of which GI and GII are responsible for the majority of norovirus infections in humans. We cloned and expressed proteases of Norwalk virus (GI) and MD145 virus (GII) and characterized the enzymatic activities with fluorescence resonance energy transfer substrates. We demonstrated that the GI and GII proteases cleaved the substrates derived from the naturally occurring cleavage site in the open reading frame (ORF) 1 of G1 norovirus with similar efficiency, and that enzymatic activity of both proteases was inhibited by commercial protease inhibitors including chymostatin. The interaction of chymostatin to Norwalk virus protease was validated by nuclear magnetic resonance (NMR) spectroscopy.


title: Epidemiological, clinical, and virological characteristics of 465 hospitalized cases of coronavirus disease 2019 (COVID‐19) from Zhejiang province in China

text: BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the associated coronavirus disease (COVID‐19) have spread throughout China. Previous studies predominantly focused on its place of origin, Wuhan, causing over estimation of the disease severity due to selection bias. We analyzed 465 confirmed cases in Zhejiang province to determine the epidemiological, clinical, and virological characteristics of COVID‐19. METHODS: Epidemiological, demographic, clinical, laboratory, and management data from qRT‐PCR confirmed COVID‐19 patients from January 17, 2020, to January 31, 2020, were collected, followed by multivariate logistic regression analysis for independent predictors of severe/critical‐type COVID‐19 and bioinformatic analysis for features of SARS‐CoV‐2 from Zhejiang province. RESULTS: Among 465 COVID‐19 patients, median age was 45 years, while hypertension, diabetes, and chronic liver disease were the most common comorbidities. History of exposure to the epidemic area was present in 170 (36.56%) and 185 (39.78%) patients were clustered in 77 families. Severe/critical‐type of COVID‐19 developed in 49 (10.54%) patients. Fever and cough were the most common symptoms, while diarrhea/vomiting was reported in 58 (12.47%) patients. Multivariate analysis revealed eight risk factors for severe/critical COVID‐19. Glucocorticoids and antibiotics were administered to 60 (12.90%) and 218(46.88%) patients, respectively. Bioinformatics showed four single amino acid mutations and one amino acid position loss in SARS‐CoV‐2 from Zhejiang province, with more similarity to humans than to viruses. CONCLUSIONS: SARS‐CoV‐2 showed virological mutations and more human transmission in Zhejiang province, indicating considerable epidemiological and clinical changes. Caution in glucocorticoid and antibiotics use is advisable.


docid: rcyyanqa

title: Critical Care Transesophageal Echocardiography in Patients During The COVID-19 Pandemic

text: The COVID-19 pandemic has placed an extraordinary strain on healthcare systems across North America. Defining the optimal approach for managing a critically ill COVID-19 patient is rapidly changing. Goal-directed transesophageal echocardiography (TEE) is frequently used by physicians caring for intubated critically-ill patients as a reliable imaging modality that is well-suited to answer questions at bedside. A multi-disciplinary group of experts in point-of-care echocardiography and TEE representing intensive care, critical care cardiology and emergency medicine from the United States and Canada, convened to review the available evidence, share experiences, and produce a consensus statement aimed to provide clinicians with a framework to maximize the safety of patients and healthcare providers when considering TEE in critically ill patients during the COVID-19 pandemic. While transthoracic echocardiography (TTE) can provide the information needed in most patients, there are specific scenarios in which TEE represents the modality of choice. Among other critical care applications, TEE can allow hemodynamic assessment of patients during prone ventilation, perform serial evaluations of the lungs during recruitment maneuvers, guide cardiac arrest resuscitation, and facilitate veno-venous extra corporeal membrane oxygenation (VV-ECMO) cannulation. To aid other clinicians in performing TEE during the COVID-19 pandemic, we describe a set of principles and practical aspects for performing examinations with a focus on the logistics, personnel, equipment required before, during, and after an examination. In the right clinical scenario, TEE is a tool that can provide the information needed to deliver the best and safest possible care for the critically ill patient.


COVID‐19: The heart of the issue


title: Rethinking interleukin-6 blockade for treatment of COVID-19

text: Interleukin-6 (IL-6) is a pleiotropic cytokine with effects in immune regulation, inflammation, and infection. The use of drugs that inhibit IL-6 biological activity has been proposed as a treatment for patients with Coronavirus Disease 2019 (COVID-19). The rationale for this approach includes commitment to the concept that inflammation is a cause of lung damage in COVID-19 and belief that IL-6 is a pro-inflammatory molecule. Observational data thought to support IL-6 inhibition include elevated circulating IL-6 levels in COVID-19 patients and association between elevated IL-6 and poor clinical outcomes. However, IL-6 has significant anti-inflammatory properties, which calls into question the rationale for employing IL-6 blockade to suppress inflammation-induced tissue injury. Also, studies suggesting a beneficial role for IL-6 in the host response to infection challenge the strategy of using IL-6 blockade to treat COVID-19. In studies of recombinant IL-6 injected into human volunteers, IL-6 levels exceeding those measured in COVID-19 patients have been observed with no pulmonary adverse events or other organ damage. These observations question the role of IL-6 as a contributing factor in COVID-19. Clinical experience with IL-6 receptor antagonists such as tocilizumab demonstrates increase in severe and opportunistic infections, raising concern about using tocilizumab and similar agents to treat COVID-19. Trials of drugs to inhibit IL-6 activity in COVID-19 are ongoing and will shed light on the role of IL-6 in COVID-19 pathogenesis. However, until more information is available, providers should exercise caution in prescribing these therapies given the potential for patient harm.


title: VACCINATIONS | Viral

text: Vaccines are preparations of weakened or killed viruses or viral subunits that trigger specific protective immunity. Vaccination is the single most effective tool for preventing communicable disease, highlighted by the achievements of the smallpox and poliomyelitis eradication programs and the rise in infections for which no effective vaccine is available: human immunodeficiency virus, malaria, worms, and tuberculosis. World Health Organization initiatives target acute respiratory diseases in infancy and early childhood with novel immunization approaches. Effective vaccines are needed urgently for viral respiratory diseases, but progress has been disappointingly slow. Vaccine candidates often show reduced efficacy in infancy, in partially immune adults, the immunocompromised, and the elderly. However, several promising vaccines are in clinical trial, and it is likely that vaccines against respiratory syncytial virus and parainfluenza will be licensed within the next 5–10 years. Mucosally delivered influenza vaccine is now available, and novel adjuvants offer the prospect of better immunogenicity. Ideally, multivalent mucosal vaccines will be developed that provide protection against a spectrum of respiratory infections in specific target age groups.


title: Drug repurposing for breast cancer therapy: Old weapon for new battle

text: Abstract Despite tremendous resources being invested in prevention and treatment, breast cancer remains a leading cause of cancer deaths in women globally. The available treatment modalities are very costly and produces severe side effects. Drug repurposing that relate to new uses for old drugs has emerged as a novel approach for drug development. Repositioning of old, clinically approved, off patent non-cancer drugs with known targets, into newer indication is like using old weapons for new battle. The advances in genomics, proteomics and information computational biology has facilitated the process of drug repurposing. Repositioning approach not only fastens the process of drug development but also offers more effective, cheaper, safer drugs with lesser/known side effects. During the last decade, drugs such as alkylating agents, anthracyclins, antimetabolite, CDK4/6 inhibitor, aromatase inhibitor, mTOR inhibitor and mitotic inhibitors has been repositioned for breast cancer treatment. The repositioned drugs have been successfully used for the treatment of most aggressive triple negative breast cancer. The literature review suggest that serendipity plays a major role in the drug development. This article describes the comprehensive overview of the current scenario of drug repurposing for the breast cancer treatment. The strategies as well as several examples of repurposed drugs are provided. The challenges associated with drug repurposing are discussed.


Ebola virus disease: the ‘Black Swan’ in West Africa


title: Intravenous sufentanil-midazolam versus sevoflurane anaesthesia in medetomidine pre-medicated Himalayan rabbits undergoing ovariohysterectomy

text: Abstract Objective To compare physiological effects of sufentanil-midazolam with sevoflurane for surgical anaesthesia in medetomidine premedicated rabbits. Study design Prospective, randomized controlled experimental study. Animals Eighteen female Himalayan rabbits, weight 2.1 ± 0.1 kg. Methods Premedication with 0.1 mg kg−1 medetomidine and 5 mg kg−1 carprofen subcutaneously, was followed by intravenous anaesthetic induction with sufentanil (2.3 μg mL−1) and midazolam (0.45 mg mL−1). After endotracheal intubation, anaesthesia was maintained with sufentanil-midazolam (n = 9) or sevoflurane (n = 9). Ovariohysterectomy was performed. Intermittent positive pressure ventilation was performed as required. Physiological variables were studied perioperatively. Group means of physiologic data were generated for different anaesthetic periods. Data were compared for changes from sedation, and between groups by anova. Post-operatively, 0.05 mg kg−1 buprenorphine was administered once and 5 mg kg−1 carprofen once daily for 2–3 days. Rabbits were examined and weighed daily until one week after surgery. Results Smooth induction of anaesthesia was achieved within 5 minutes. Sufentanil and midazolam doses were 0.5 μg kg−1 and 0.1 mg kg−1, during induction and 3.9 μg kg−1 hour−1 and 0.8 mg kg−1 hour−1 during surgery, respectively. End-tidal sevoflurane concentration was 2.1% during surgery. Assisted ventilation was required in nine rabbits receiving sufentanil-midazolam and four receiving sevoflurane. There were no differences between groups in physiologic data other than arterial carbon dioxide. In rabbits receiving sevoflurane, mean arterial pressure decreased pre-surgical intervention, heart rate increased 25% during and after surgery and body weight decreased 4% post-operatively. Post-operative problems sometimes resulted from catheterization of the ear artery. Conclusion Sevoflurane and sufentanil-midazolam provided surgical anaesthesia of similar quality. Arterial blood pressure was sustained during sufentanil-midazolam anaesthesia and rabbits receiving sevoflurane lost body weight following ovariohysterectomy. Mechanical ventilation was required with both anaesthetic regimens. Clinical relevance Anaesthesia with sufentanil-midazolam in medetomidine premedicated healthy rabbits is useful in the clinical and the research setting, as an alternative to sevoflurane.


title: Anti-inflammatory and Antimicrobial Effects of Heat-clearing Chinese Herbs: A Current Review

text: ABSTRACT Inflammation is a normal immune response; but if the body’s regulation of inflammation is dysfunctional, then it will have an adverse effect on the body. Although use of modern drugs for inflammation has a relieving effect, it is still unsatisfactory. Moreover, the emergence of drug-resistant strains and even new kinds of microorganisms is causing significant morbidity and mortality. Recently, more attention has been focused on herbal medicine to treat various diseases because of the ability of the herbs to affect multiple target signaling pathways and their multiple mechanisms of action. Thus, a large number of studies have reported on the anti-inflammatory and antimicrobial effects of the traditional Chinese herbs. Literature survey was performed by conducting systematic electronic search in PubMed, Science Direct, Google Scholar, and in books. This review has listed 11 heat-clearing Chinese herbs (HCCHs) including Scutellaria baicalensis (黃芩 Huáng Qín), Coptis chinensis (黃連 Huáng Lián), Flos Lonicerae (金銀花 Jīn Yín Hūa), Forsythia suspensa (連翹 Lián Qiào), Isatidis Folium (大青葉 Dà Qīn Yè), Radix Isatidis (板藍根 Bǎn Lán Gēn), Viola yedoensis (紫花地丁 Zǐ Huā Dì Dīn), Pulsatilla Radix (白頭翁 Bái Tóu Wēn), Andrographis paniculata (穿心蓮 Chuān Xīn Lián), Houttuynia cordata (魚腥草 Yú Xīng Cǎo), and Patrinia Herba (敗醬草 Bài Jiàn Cǎo), which have anti-inflammatory and antimicrobial effects, and has described their effects through different mechanisms of action and multiple targets. Their ability to affect multiple target signaling pathways and their potential mechanisms of action contributing to their anti-inflammatory and antimicrobial activity may be related to their action of removing heat and counteracting toxicity. Further studies are needed on the collection of HCCHs to know the detailed mechanism of action of herbs in this group for the assessment of effective drug.


title: Buffalo: Asia ☆

text: Abstract Domestic buffaloes (Bubalus bubalis) of swamp type (for draught) and river type (for milk) dominate the tropical Asia with slightly more than 169.4 million. They breed throughout the year and produce two calves every 3 years and are fed mainly on straw, crop residues, and mineral supplements. Assisted reproductive technologies such as artificial insemination and embryo transfer have also been introduced and implemented in buffalo production with less success due to difficulty in detecting estrus. Providing good feed and feeding remain a challenge in buffalo husbandry due to limited feed resources. With improved management and proper breeding, the milk production from buffaloes has increased from 1500 to 5000l per lactation. The river type buffalo currently produces about 73.2 million tonnes of milk annually.


title: Respiratory syncytial virus subtype ON1/NA1/BA9 predominates in hospitalized children with lower respiratory tract infections

text: Respiratory syncytial virus (RSV) infection is the leading cause of acute respiratory tract disease in children less than 5 years old. The aim of this study was to further elucidate the molecular properties and clinical characteristics of RSV infection. The study sample included 238 patients <5 years old who were hospitalized with clinical symptoms of upper or lower respiratory tract infection (URTI or LRTI) in the Pediatric Department at the First People's Hospital of Chenzhou, South China in 2014. We subjected nasopharyngeal aspirate (NPA) or nasal swab (NS) samples from the patients to indirect fluorescence assay screens. RSV G genes were amplified by reverse transcription‐PCR (RT‐PCR) and sequenced. Of the 238 patients screened, 64 (26.8%) were confirmed to have RSV infections. Of those 64 confirmed RSV infection cases, 39 (60.9%) had subtype BA9, 13 (20.3%) had the recently identified subtype ON1, 11 (17.2%) had subtype NA1, and 1 (1.6%) had subtype GB2. The predominant presentation was LRTI with coughing, sputum production, fever, and wheezing. RSV subtype NA1 and BA9 infections were found mostly in infants, whereas the age distribution of subtype ON1 infections was more uniform across the age bands. Phylogenetic analysis indicated that, compared with the prototype strain A2, all ON1 and most NA1 isolates had lost one potential N‐glycosylation site at amino acid 251 and 249 due to T251K and N249Y substitution, respectively. These findings suggest that NA1, BA9, and ON1 are the dominant RSV subtypes causing respiratory tract infections in young children presenting to the hospital in South China. J. Med. Virol. 89:213–221, 2017. © 2016 Wiley Periodicals, Inc.


title: Innate immunogenetics: a tool for exploring new frontiers of host defence

text: Summary The discovery of innate immune genes, such as those encoding Toll-like receptors (TLRs), nucleotide-binding oligomerisation domain-like receptors (NLRs), and related signal-transducing molecules, has led to a substantial improvement of our understanding of innate immunity. Recent immunogenetic studies have associated polymorphisms of the genes encoding TLRs, NLRs, and key signal-transducing molecules, such as interleukin-1 receptor-associated kinase 4 (IRAK4), with increased susceptibility to, or outcome of, infectious diseases. With the availability of high-throughput genotyping techniques, it is becoming increasingly evident that analyses of genetic polymorphisms of innate immune genes will further improve our knowledge of the host antimicrobial defence response and help in identifying individuals who are at increased risk of life-threatening infections. This is likely to open new perspectives for the development of diagnostic, predictive, and preventive management strategies to combat infectious diseases.


title: A systematic review on silver nanoparticles-induced cytotoxicity: Physicochemical properties and perspectives

text: With the development of nanotechnology, silver nanoparticles (Ag-NPs) have become one of the most in-demand nanoparticles owing to their exponential number of uses in various sectors. The increased use of Ag-NPs-enhanced products may result in an increased level of toxicity affecting both the environment and living organisms. Several studies have used different model cell lines to exhibit the cytotoxicity of Ag-NPs, and their underlying molecular mechanisms. This review aimed to elucidate different properties of Ag-NPs that are responsible for the induction of cellular toxicity along with the critical mechanism of action and subsequent defense mechanisms observed in vitro. Our results show that the properties of Ag-NPs largely vary based on the diversified synthesis processes. The physiochemical properties of Ag-NPs (e.g., size, shape, concentration, agglomeration, or aggregation interaction with a biological system) can cause impairment of mitochondrial function prior to their penetration and accumulation in the mitochondrial membrane. Thus, Ag-NPs exhibit properties that play a central role in their use as biocides along with their applicability in environmental cleaning. We herein report a current review of the synthesis, applicability, and toxicity of Ag-NPs in relation to their detailed characteristics.


title: The N-95 mask: invaluable ally in the battle against the COVID-19 pandemic

text: The present COVID-19 pandemic, caused by the airborne SARS-CoV-2 virus, has highlighted the vital importance of appropriate personal protective equipment for all exposed health care workers The single most important part of this armor is the N-95 mask With the awareness that the virus is spread by both droplets and through the aerosolized route, the N-95 provides protection that a surgical mask cannot match This timely review looks at the special advantages that an N-95 offers over a surgical mask with specific reference to the COVID-19 epidemic It also emphasizes the crucial importance of ensuring quality masks with a proper fit Finally, with acute scarcities of N-95 masks being reported from hospitals globally, it reviews recent literature which attempts to prolong the life of these masks with extended use, reuse and decontamination of used masks


title: Functional Properties of the Predicted Helicase of Porcine Reproductive and Respiratory Syndrome Virus

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is a member of the positive-strand RNA virus family Arteriviridae. Although considerable research has focused on this important pathogen, little is known about the function of most PRRSV proteins. To examine characteristics of putative nonstructural proteins (nsp) encoded in ORF1b, which have been identified by nucleotide similarity to domains of equine arteritis virus, defined genomic regions were cloned and expressed in the pRSET expression system. One region, nsp10, encoded a protein with a putative helicase domain and was further examined for functional helicase-like activities. PRRSV nsp10 was found to possess a thermolabile and pH-sensitive NTPase activity that was modulated by polynucleotides and to unwind dsRNA in a 5′ to 3′ polarity. These results provide the first evidence of the functional properties of PRRSV helicase and further support the finding that nidovirus helicases possess properties that distinguish them from other viral helicases.


title: Mechanisms of Antiviral Activity of Iminosugars Against Dengue Virus

text: The antiviral mechanism of action of iminosugars against many enveloped viruses, including dengue virus (DENV), HIV, influenza and hepatitis C virus, is believed to be mediated by inducing misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum-resident α-glucosidase enzymes. This leads to reduced secretion and/or infectivity of virions and hence lower viral titres, both in vitro and in vivo. Free oligosaccharide analysis from iminosugar-treated cells shows that antiviral activity correlates with production of mono- and tri-glucosylated sugars, indicative of inhibition of ER α-glucosidases. We demonstrate that glucose-mimicking iminosugars inhibit isolated glycoprotein and glycolipid processing enzymes and that this inhibition also occurs in primary cells treated with these drugs. Galactose-mimicking iminosugars that have been tested do not inhibit glycoprotein processing but do inhibit glycolipid processing, and are not antiviral against DENV. By comparison, the antiviral activity of glucose-mimetic iminosugars that inhibit endoplasmic reticulum-resident α-glucosidases, but not glycolipid processing, demonstrates that inhibition of α-glucosidases is responsible for iminosugar antiviral activity against DENV. This monograph will review the investigations of many researchers into the mechanisms of action of iminosugars and the contribution of our current understanding of these mechanisms for optimising clinical delivery of iminosugars. The effects of iminosugars on enzymes other than glucosidases, the induction of ER stress and viral receptors will be also put into context. Data suggest that inhibition of α-glucosidases results in inhibited release of virus and is the primary antiviral mechanism of action of iminosugars against DENV.


docid: ucsqsjhi

title: Implication of proprotein convertases in the processing and spread of severe acute respiratory syndrome coronavirus

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS. Analysis of SARS-CoV spike glycoprotein (S) using recombinant plasmid and virus infections demonstrated that the S-precursor (proS) exists as a ∼190 kDa endoplasmic reticulum form and a ∼210 kDa Golgi-modified form. ProS is subsequently processed into two C-terminal proteins of ∼110 and ∼80 kDa. The membrane-bound proprotein convertases (PCs) furin, PC7 or PC5B enhanced the production of the ∼80 kDa protein. In agreement, proS processing, cytopathic effects, and viral titers were enhanced in recombinant Vero E6 cells overexpressing furin, PC7 or PC5B. The convertase inhibitor dec-RVKR-cmk significantly reduced proS cleavage and viral titers of SARS-CoV infected cells. In addition, inhibition of processing by dec-RVKR-cmk completely abrogated the virus-induced cellular cytopathicity. A fluorogenically quenched synthetic peptide encompassing Arg(761) of the spike glycoprotein was efficiently cleaved by furin and the cleavage was inhibited by EDTA and dec-RVKR-cmk. Taken together, our data indicate that furin or PC-mediated processing plays a critical role in SARS-CoV spread and cytopathicity, and inhibitors of the PCs represent potential therapeutic anti-SARS-CoV agents.


title: IgA-Ab response to spike glycoprotein of SARS-CoV-2 in patients with COVID-19: A longitudinal study

text: Abstract Validation studies of serological antibody tests must be properly designed for clinical, epidemiological and Public Health objectives such as confirmation of suspected COVID-19 cases, certification of seroconversion after infection, and epidemiological surveillance. We evaluated the kinetics of IgM, IgA and IgG SARS-CoV-2 antibodies in COVID-19 patients with confirmed (rRT-PCR) infection. We found that the IgA response appears and grows early, peaks at week 3, and it is stronger and more persistent than the IgM response. Further longitudinal investigations of virus-specific antibodies functions and of their protective efficacy over time are needed.


title: Immune responses and pathogenesis in persistently PCR‐positive patients with SARS‐CoV‐2 infection

text: Coronavirus disease (COVID‐19) caused by SARS‐CoV‐2 emerged in China in December 2019 and then rapidly spread worldwide. Why COVID‐19 patients with the same clinical condition have different outcomes remains unclear. This study aimed to examine the differences in the phenotype and functions of major populations of immune cells between COVID‐19 patients with same severity but different outcomes. Four common type adult inpatients with laboratory confirmed COVID‐19 from Beijing YouAn Hospital, Capital Medical University were included in this study. The patients were divided into two groups based on whether or not COVID‐19 PCR‐negative conversion occurred within three weeks. Peripheral blood samples were collected to compare the differences in the phenotype and functions of major populations of immune cells between the two groups of patients. The result shows that the proportions of CD3(+)CD8(+)CD38(+)HLA‐DR(+)CD27(‐) effector T killer cells generally declined, whereas that of CD3(+)CD4(+)CD8(+) double‐positive T cells (DPTs) increased in the persistently PCR‐positive patients. In summary, considering the imbalance between effector T killer cells/ CD3+CD4+CD8+ DPTs was a possible key factor for PCR‐negative conversion in COVID‐19 patients. This article is protected by copyright. All rights reserved.


title: Detecting Viral Outbreaks in Future Using Enhanced Environmental Surveillance

text: • Severe Acute Respiratory Syndrome Coronavirus 2 can be detected in the sewage system. • Sewage surveillance can estimate disease burden and recurrent epidemic dynamics. • Enhanced surveillance on sewage system can identify early warning calls.


title: Previous Hepatitis A Virus Infection Is Related to Slower Psychomotor Speed in Elderly Adults

text: BACKGROUND: Patients with chronic viral hepatitis are at a higher risk for cognitive dysfunction. Little is known about the association between hepatitis A virus (HAV) infection and cognitive function. METHODS: From the National Health and Nutrition Examination Survey, 1999–2002, we selected study participants (≥60 years, n = 1,529) without hepatitis B, C, or D virus infection; without previous hepatitis A vaccination; and without abnormal liver function. HAV-seropositive participants represented people with previous HAV infection. Psychomotor speed and executive functioning domain of cognitive function were measured by the Digit Symbol Substitution Test (DSST). RESULTS: HAV-seropositive participants had lower DSST scores than HAV-seronegative participants (weighted mean, 44.4 vs 53.9, p < .001). We designated HAV-seronegative participants as the reference group. Univariate analysis demonstrated that the weighted β coefficient of DSST score was −9.55 (95% confidence interval [CI] −9.57 to −9.54, p < .001) for the HAV-seropositive participants. In a multivariable model, the weighted adjusted β coefficient of DSST score was −2.48 (95% CI −2.49 to −2.46, p < .001) for the HAV-seropositive participants. CONCLUSION: HAV seropositivity is associated with slower psychomotor speed among the U.S. community-dwelling elders.


‘Led by the science’, evidence gaps, and the risks of aerosol transmission of SARS-COV-2


title: Design and validation of consensus-degenerate hybrid oligonucleotide primers for broad and sensitive detection of corona- and toroviruses

text: Abstract The ssRNA+ family Coronaviridae includes two subfamilies prototyped by coronaviruses and toroviruses that cause respiratory and enteric infections. To facilitate the identification of new distantly related members of the family Coronaviridae, we have developed a molecular assay with broad specificity. The consensus-degenerated hybrid oligonucleotide primer (CODEHOP) strategy was modified to design primers targeting the most conserved motifs in the RNA-dependent RNA polymerase locus. They were evaluated initially on RNA templates from virus-infected cells using a two-step RT-PCR protocol that was further advanced to a one-step assay. The sensitivity of the assay ranged from 102 to 106 and from 105 to 109 RNA copy numbers for individual corona-/torovirus templates when tested, respectively, with and without an excess of RNA from human cells. This primer set compared to that designed according to the original CODEHOP rules showed 10–103 folds greater sensitivity for 5 of the 6 evaluated corona-/torovirus templates. It detected 57% (32 of 56) of the respiratory specimens positive for 4 human coronaviruses, as well as stool specimens positive for a bovine torovirus. The high sensitivity and broad virus range of this assay makes it suitable for screening biological specimens in search for new viruses of the family Coronaviridae.


docid: tonamcth

title: ANTIBODY FUSIONS REDUCE ONSET OF EXPERIMENTAL CRYPTOSPORIDIUM PARVUM INFECTION IN CALVES

text: Cryptosporidium parvum is one of the main causes of diarrhea in neonatal calves resulting in significant morbidity and economic losses for producers worldwide. We have previously demonstrated efficacy of a new class of antimicrobial antibody fusions in a neonatal mouse model for C. parvum infection. Here, we extend efficacy testing of these products to experimental infection in calves, the principal target species. Neonatal calves were challenged with C. parvum oocysts and concomitantly treated with antibody-biocide fusion 4H9-G1-LL37 over the course of four days. This resulted in reduced severity of the disease when compared to control animals. Overall clinical health parameters showed significant improvement in treated animals. Oocyst shedding was reduced in treated when compared to control animals. Control of oocyst shedding is a prerequisite for breaking the cycle of re-infection on dairy farms. Antibody-biocide fusion products thus have the potential to reduce the impact of the infection in both individual animals and in the herd.


title: Chilblains‐like lesions and COVID‐19

text: The publication entitled “Chilblains‐like lesions in children following suspected Covid‐19 infection” is very interesting [1]. Colonna et al. reported four children with suspected COVID‐19 cases with “[h]istology from one case showed signs of vasculitis with evident fibrin thrombus [1].” While various skin findings have been reported with COVID‐19 infection, the chilblains lesions have been reported from Italy and Spain, and sporadically from China, the starting point of disease pandemic [2‐5].


title: Standardized Testing Demonstrates Altered Odor Detection Sensitivity and Hedonics in Asymptomatic College Students as SARS-CoV-2 Emerged Locally

text: BACKGROUND: Anosmia is a recognized symptom of COVID-19, but the relationship of SARS-CoV-2 exposure with olfactory dysfunction remains enigmatic. This report adds unique data from healthy students tested as the virus emerged locally. METHODS: Standard psychometric measures assessed odor detection, identification and hedonics in healthy university students. Data from asymptomatic students (N=22), tested as SARS-CoV-2 unknowingly emerged locally, were compared to students tested just prior to local virus transmission (N=25), and our normative sample (N=272) tested over the previous 4 years. RESULTS: The exposed cohort demonstrated significantly reduced odor detection sensitivity compared to the students in the prior group (P=.01; d=0.77; CI 0.17, 1.36), with a distribution skewed towards less detection sensitivity (P=.03). Categorically, the exposed group was significantly more likely to have hyposmia (OR=7.7; CI, 3.1, 19.4), particularly the subset assessed in the final week before campus closure (OR=13.6; CI, 3.4, 35.7). The exposed group also rated odors as less unpleasant (P<.001, CLES=0.77, CI, 0.51, 1.56) which also showed a skewed distribution (P=.005). The groups had similar odor identification performance. CONCLUSION: Psychometric measures of odor detection sensitivity and hedonics may detect early SARS-CoV-2 exposure in asymptomatic and pre-symptomatic persons with normal odor identification. Viral detection by nasal associated lymphoid tissue is known to trigger systemic immune effects, but its activation may also reduce smell sensitivity and shift perception of the environment towards unpleasant, increasing the social isolation that may mitigate viral infection or transmission. Regular testing of odor detection and hedonics may have value for identifying regional viral exposure.


title: Evolutionary implications of Avian Infectious Bronchitis Virus (AIBV) analysis

text: For developing efficient vaccines, it is essential to identify which amino acid changes are most important to the survival of the virus. We investigate the amino acid substitution features in the Avian Infectious Bronchitis Virus (AIBV) antigenic domain of a vaccine serotype (DE072) and a virulent viral strain (GA98) to better understand adaptive evolution of AIBV. In addition, the SARS Coronavirus (SARS-CoV) was also analyzed in the same way. It is interesting to find that extreme comparability exists between AIBV and SARS in amino acid substitution pattern. It suggests that amino acid changes that result in overall shift of residue charge and polarity should be paid special attention to during the development of vaccines.