title: Immunological aspects of the efficiency of protectotype vaccination strategy against chicken infectious bronchitis

text: BACKGROUND: One of the most commonly applied protectotype vaccination protocol against infectious bronchitis (IB) in broiler chickens in the EU is simultaneous or alternate use of Ma5 and 4/91 vaccine strains. After IB vaccination and infection, systemic and upper respiratory tract (URT), humoral and cell-mediated immunity (CMI), are stimulated. The level of this stimulation correlates with the level of protection against IB. RESULTS: We’ve investigated the development of URT and systemic, cell-mediated and humoral immunity in commercial broiler chickens vaccinated with Ma5 and/or 4/91 strains at hatch day. We’ve demonstrated that the group vaccinated with Ma5 and 4/91 strain simultaneously developed the most desirable immunity which reflects the level of CD8(+) T cells stimulation in spleen and Harderian gland, as well as the level of IgA and IgY in URT washings and serum and their cross-reactivity with 7 IBV strains. CONCLUSIONS: Although we did not demonstrate directly why Ma5 + 4/91 protocol is so efficient it seems that it combines the benefits of monovalent vaccination with either Ma5 or 4/91 and while Ma5 seems to stimulate CMI more efficiently, the 4/91 strain generates a wider spectrum of immune system cross-reactivity and higher URT IgA production.


title: Relationships between cold-temperature indices and all causes and cardiopulmonary morbidity and mortality in a subtropical island

text: Abstract This study aimed to identify optimal cold-temperature indices that are associated with the elevated risks of mortality from, and outpatient visits for all causes and cardiopulmonary diseases during the cold seasons (November to April) from 2000 to 2008 in Northern, Central and Southern Taiwan. Eight cold-temperature indices, average, maximum, and minimum temperatures, and the temperature humidity index, wind chill index, apparent temperature, effective temperature (ET), and net effective temperature and their standardized Z scores were applied to distributed lag non-linear models. Index-specific cumulative 26-day (lag 0–25) mortality risk, cumulative 8-day (lag 0–7) outpatient visit risk, and their 95% confidence intervals were estimated at 1 and 2 standardized deviations below the median temperature, comparing with the Z score of the lowest risks for mortality and outpatient visits. The average temperature was adequate to evaluate the mortality risk from all causes and circulatory diseases. Excess all-cause mortality increased for 17–24% when average temperature was at Z=−1, and for 27–41% at Z=−2 among study areas. The cold-temperature indices were inconsistent in estimating risk of outpatient visits. Average temperature and THI were appropriate indices for measuring risk for all-cause outpatient visits. Relative risk of all-cause outpatient visits increased slightly by 2–7% when average temperature was at Z=−1, but no significant risk at Z=−2. Minimum temperature estimated the strongest risk associated with outpatient visits of respiratory diseases. In conclusion, the relationships between cold temperatures and health varied among study areas, types of health event, and the cold-temperature indices applied. Mortality from all causes and circulatory diseases and outpatient visits of respiratory diseases has a strong association with cold temperatures in the subtropical island, Taiwan.


title: Electron Microscopy in Discovery of Novel and Emerging Viruses from the Collection of the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA)

text: Since the beginning of modern virology in the 1950s, transmission electron microscopy (TEM) has been an important and widely used technique for discovery, identification and characterization of new viruses. Using TEM, viruses can be differentiated by their ultrastructure: shape, size, intracellular location and for some viruses, by the ultrastructural cytopathic effects and/or specific structures forming in the host cell during their replication. Ultrastructural characteristics are usually sufficient for the identification of a virus to the family level. In this review, we summarize 25 years of experience in identification of novel viruses from the collection of the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA).


title: The spleen morphophysiology of fruit bats

text: Spleen is one of the important lymphoid organs with wide variations of morphological and physiological functions according to species. Morphology and function of the spleen in bats, which are hosts to several viral strains without exhibiting clinical symptoms, remain to be fully elucidated. This study aims to examine the spleen morphology of fruit bats associated with their physiological functions. Spleen histological observations were performed in three fruit bats species: Cynopterus titthaecheilus (n = 9), Rousettus leschenaultii (n = 3) and Pteropus vampyrus (n = 3). The spleens of these fruit bats were surrounded by a thin capsule. Red pulp consisted of splenic cord and wide vascular space filled with blood. Ellipsoids in all three studied species were found numerously and adjacent to one another forming macrophages aggregates. White pulp consisted of periarteriolar lymphoid sheaths (PALS), lymphoid follicles and marginal zone. The lymphoid follicle contained a germinal centre and a tingible body macrophage that might reflect an active immune system. The marginal zone was prominent and well developed. This study reports some differences in spleen structure of fruit bats compared to other bat species previously reported and discusses possible physiological implications of the spleen based on its morphology.


title: Rapamycin-induced autophagy restricts porcine epidemic diarrhea virus infectivity in porcine intestinal epithelial cells

text: Abstract Porcine epidemic diarrhea virus (PEDV) invades porcine intestinal epithelial cells (IECs) and causes diarrhea and dehydration in pigs. In the present study, we showed a suppression of PEDV infection in porcine jejunum intestinal epithelial cells (IPEC-J2) by an increase in autophagy. Autophagy was activated by rapamycin at a dose that does not affect cell viability and tight junction permeability. The induction of autophagy was examined by LC3I/LC3II conversion. To confirm the autophagic-flux (entire autophagy pathway), autophagolysosomes were examined by an immunofluorescence assay. Pre-treatment with rapamycin significantly restricted not only a 1 h infection but also a longer infection (24 h) with PEDV, while this effect disappeared when autophagy was blocked. Co-localization of PEDV and autophagosomes suggests that PEDV could be a target of autophagy. Moreover, alleviation of PEDV-induced cell death in IPEC-J2 cells pretreated with rapamycin demonstrates a protective effect of rapamycin against PEDV-induced epithelial cell death. Collectively, the present study suggests an early prevention against PEDV infection in IPEC-J2 cells via autophagy that might be an effective strategy for the restriction of PEDV, and opens up the possibility of the use of rapamycin in vivo as an effective prophylactic and prevention treatment.


Riesgo de reactivación de la hepatitis B asociado al tratamiento con corticoides frente a SARS-CoV-2 (COVID-19)


title: Induction of interleukin-8 by Naegleria fowleri lysates requires activation of extracellular signal-regulated kinase in human astroglial cells

text: Naegleria fowleri is a pathogenic free-living amoeba which causes primary amoebic meningoencephalitis in humans and experimental animals. To investigate the mechanisms of such inflammatory diseases, potential chemokine gene activation in human astroglial cells was investigated following treatment with N. fowleri lysates. We demonstrated that N. fowleri are potent inducers for the expression of interleukin-8 (IL-8) genes in human astroglial cells which was preceded by activation of extracellular signal-regulated kinase (ERK). In addition, N. fowleri lysates induces the DNA binding activity of activator protein-1 (AP-1), an important transcription factor for IL-8 induction. The specific mitogen-activated protein kinase kinase/ERK inhibitor, U0126, blocks N. fowleri-mediated AP-1 activation and subsequent IL-8 induction. N. fowleri-induced IL-8 expression requires activation of ERK in human astroglial cells. These findings indicate that treatment of N. fowleri on human astroglial cells leads to the activation of AP-1 and subsequent expression of IL-8 which are dependent on ERK activation. These results may help understand the N. fowleri-mediated upregulation of chemokine and cytokine expression in the astroglial cells.


title: Patterns of influenza B circulation in Brazil and its relevance to seasonal vaccine composition

text: Abstract Data on the burden of disease and circulation patterns of influenza B lineages for Brazil are limited. This review aims to describe the pattern of influenza B occurrence in Brazil to have a better understanding of its epidemiology and its relevance when considering seasonal influenza vaccine composition. A review of the data including analysis of international and local surveillance data as well as information from online search of databases using Medical Subject Headings terms in conjunction with screening of abstracts from scientific events was performed. Based on international epidemiologic surveillance data, moderate levels of influenza B disease (19%; 2006–2014) were observed. Of these nine years, it was possible to compare data from three years (2007, 2008 and 2013) which have information on the circulating influenza B lineage. Co-circulation of influenza B lineages was observed in all these three influenza seasons, of which, during one season, a high degree of mismatch between the vaccine lineage and the predominant circulating lineage (91.4% [2013]) was observed. Local surveillance data reveal a distinct and dynamic distribution of respiratory viruses over the years. Data from published literature and abstracts show that influenza B is a significant cause of disease with an unpredictable circulation pattern and showing trends indicating reemergence of the B/Victoria lineage. The abstracts report notable levels of co-circulation of both influenza B lineages (2000–2013). Mismatch between the Southern hemisphere vaccine and the most prevalent circulating viruses in Brazil were observed in five influenza seasons. The evidence on co-circulation of two influenza B lineages and mismatched seasons in Brazil indicates the benefit of quadrivalent influenza vaccines in conferring broader seasonal influenza protection. Additionally, improving influenza surveillance platforms in Brazil is important for monitoring disease trends and the impact of introducing seasonal influenza vaccination.


title: ALTERED THEOPHYLLINE PHARMACOKINETICS DURING ACUTE RESPIRATORY VIRAL ILLNESS

text: Abstract The plasma half-life of theophylline was determined during and 1 month after serologically confirmed upper-respiratory-tract viral illness in six children with chronic asthma. In this group the plasma-theophylline half-life (mean=419·8 min) was significantly longer during the acute stage of their illness than 1 month later (mean 249·9 min). There was no appreciable change in half-life in 4 patients who were febrile but in whom seroconversion did not occur. These preliminary results suggest that certain upper-respiratory-tract viral infections may affect theophylline metabolism.


title: The correlation between viral clearance and biochemical outcomes of 94 COVID-19 infected discharged patients

text: OBJECTIVE: This study aims to evaluate the correlation between viral clearance and blood biochemical index of 94 discharged patients with COVID-19 infection in Shenzhen Third People’s Hospital, enrolled from Jan 5 to Feb 13, 2020. METHODS: The clinical and laboratory findings were extracted from the electronic medical records of the patients. The data were analysed and reviewed by a trained team of physicians. Information on clinical signs and symptoms, medical treatment, virus clearance, and laboratory parameters including interleukin 6 (IL-6) and C-reactive protein were collected. RESULTS: COVID-19 mRNA clearance ratio was identified significantly correlated with the decline of serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Furthermore, COVID-19 mRNA clearance time was positively correlated with the length of hospital stay in patients treated with either IFN-α + lopinavir/ritonavir or IFN-α + lopinavir/ritonavir + ribavirin. CONCLUSIONS: Therapeutic regimens of IFN-α + lopinavir/ritonavir and IFN-α + lopinavir/ritonavir + ribavirin might be beneficial for treatment of COVID-19. Serum LDH or CK decline may predict a favorable response to treatment of COVID-19 infection.


title: Testing for Respiratory Viruses in Adults With Severe Lower Respiratory Infection

text: Viral pathogens are a common cause of severe lower respiratory tract infection in adults. Our ability to rapidly and accurately identify viral infections has dramatically improved as slow culture-based techniques have been largely replaced by multiplex high-throughput systems. Given these advances, reevaluation of the role of respiratory viral testing in adults presenting with lower respiratory tract infection is important. This article reviews the potential benefits of testing, provides an overview of the most commonly used diagnostic techniques, and considers whether current evidence supports routine testing.


title: Complete title: Codon bias analysis may be insufficient for identifying host(s) of a novel virus

text: A novel kind of coronavirus has infected more than 1, 600, 000 people, claimed over 100, 000 lives, and spread to 212 countries and territories since December 2019.(1) The virus has been named SARS‐CoV‐2 (provisionally termed 2019‐nCoV before(2)), and the pneumonia caused by it is COVID‐19. Though many scientists and researchers are trying to identify the animals harboring SARS‐CoV‐2, the intermediate host remains under the veil. This article is protected by copyright. All rights reserved.


Care for patients with rheumatic diseases during COVID‐19 pandemic: A position statement from APLAR


title: Evaluation of humoral immune status in porcine epidemic diarrhea virus (PEDV) infected sows under field conditions

text: Porcine epidemic diarrhea virus (PEDV) is an economically devastating enteric disease in the swine industry. The virus infects pigs of all ages, but it cause severe clinical disease in neonatal suckling pigs with up to 100% mortality. Currently, available vaccines are not completely effective and feedback methods utilizing PEDV infected material has variable success in preventing reinfection. Comprehensive information on the levels and duration of effector/memory IgA and IgG antibody secreting B cell response in the intestines and lymphoid organs of PEDV-infected sows, and their association with specific antibody levels in clinical samples such as plasma, oral fluid, and feces is important. Therefore, our goal in this study was to quantify PEDV specific IgA and IgG B cell responses in sows at approximately 1 and 6 months post-infection in commercial swine herds, including parity one and higher sows. Our data indicated that evaluation of both PEDV specific IgA and IgG antibody levels in the plasma and oral fluid (but not feces) samples is beneficial in disease diagnosis. PEDV specific B cell response in the intestine and spleen of infected sows decline by 6 months, and this associates with specific antibody levels in the plasma and oral fluid samples; but the virus neutralization titers in plasma remains high beyond 6 months post-infection. In conclusion, in sows infected with PEDV the presence of effector/memory B cell response and strong virus neutralization titers in plasma up to 6 months post-infection, suggests their potential to protect sows from reinfection and provide maternal immunity to neonates, but challenge studies are required to confirm such responses.


title: Expression of the protective antigen for PEDV in transgenic duckweed, Lemna minor

text: Duckweeds are small, floating aquatic plants with a number of useful characteristics, including edibility, fast-growing, and a clonal proliferation. Duckweed is also fed to animals as a diet complement because of its high nutritional value. Porcine epidemic diarrhea virus (PEDV) is a major causative agent of fatal diarrhea in piglets and is a serious problem in the hog-raising industry. In this study, we assessed the feasibility of producing a protective antigen for the PEDV spike protein 1 using duckweed, Lemna minor. Stably transformed Lemna were obtained by co-cultivation with A. tumefaciens EHA105 harboring the PEDV spike protein gene. Transgene integration and expression of the PEDV spike protein 1 gene were confirmed by genomic PCR and RT-PCR and western blot analysis of transgenic Lemna, respectively. This is the first report of the expression of a vaccine antigen against an animal infectious disease in duckweed.


title: The Infectious Bronchitis Virus Coronavirus Envelope Protein Alters Golgi pH to Protect Spike Protein and Promote Release of Infectious Virus

text: Coronaviruses (CoVs) are important human pathogens with significant zoonotic potential. Progress has been made toward identifying potential vaccine candidates for highly pathogenic human CoVs, including use of attenuated viruses that lack the CoV envelope (E) protein or express E mutants. However, no approved vaccines or anti-viral therapeutics exist. CoVs assemble by budding into the lumen of the early Golgi prior to exocytosis. The small CoV E protein plays roles in assembly, virion release, and pathogenesis. CoV E has a single hydrophobic domain (HD), is targeted to Golgi membranes, and has cation channel activity in vitro. The E protein from the avian infectious bronchitis virus (IBV) has dramatic effects on the secretory system, which requires residues in the HD. Mutation of the HD of IBV E during infection results in impaired growth kinetics, impaired release of infectious virions, accumulation of IBV S protein on the plasma membrane when compared IBV WT infected cells, and aberrant cleavage of IBV S on the surface of virions. We previously reported the formation of two distinct oligomeric pools of IBV E in transfected and infected cells. Disruption of the secretory pathway by IBV E correlates with a form that is likely monomeric, suggesting that the effects on the secretory pathway are independent of E ion channel activity. Here, we present evidence suggesting that the monomeric form of IBV E correlates with a rise in the pH of the Golgi lumen. We demonstrate that infection with IBV induces neutralization of Golgi luminal pH, promoting a model in which IBV E alters the secretory pathway through interaction with host cells factors, protecting IBV spike protein (S) from premature cleavage and leading to the efficient release of infectious virus from the cells.


title: Clustering analysis of countries using the COVID-19 cases dataset

text: There is a worldwide effort of the research community to explore the medical, economic and sociologic impact of the COVID-19 pandemic. Many different disciplines try to find solutions and drive strategies to a great variety of different very crucial problems. The present study presents a novel analysis which results to clustering countries with respect to active cases, active cases per population and active cases per population and per area based on Johns Hopkins epidemiological data. The presented cluster results could be useful to a variety of different policy makers, such as physicians and managers of the health sector, economy/finance experts, politicians and even to sociologists. In addition, our work suggests a new specially designed clustering algorithm adapted to the request for comparison of the various COVID time-series of different countries.


title: Influenza‐like illnesses caused by a cluster of imported Italian COVID‐19

text: The ongoing pandemic of 2019 corona‐virus disease (COVID‐19) is caused by an emerging family of SARS‐CoV‐2, threatening human health worldwide. Here we report a cluster of Italian COVID‐19 imported to Lishui City, China. Of all the eight patients, 7 consistently display cough, a representative sign of influenza‐like illness (ILI), and the remaining one is a cryptic case. This further our understanding a full spectrum of COVID‐19 repertoire. This article is protected by copyright. All rights reserved.


title: Feasibility of a randomized controlled trial to assess treatment of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Saudi Arabia: a survey of physicians

text: BACKGROUND: The Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging respiratory pathogen with a high mortality rate and no specific treatments available to date. The purpose of this study was to determine the feasibility of conducting a randomized controlled trial (RCT) of convalescent plasma therapy for MERS-CoV-infected patients by using MERS-CoV-specific convalescent plasma obtained from previously recovered patients. METHODS: A survey was adapted from validated questionnaire originally aimed to measure network capacities and capabilities within the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC). The questionnaire was modified for this study to include 26 items that were divided into three main domains of interest: (1) the ability to care for critically ill MERS-CoV patients; (2) laboratory capacity to diagnose MERS-CoV and blood bank ability to prepare convalescent plasma; and (3), research capacity to conduct randomized controlled trials. The questionnaire was emailed to physicians. RESULTS: Of 582 physicians who were invited to the survey, 327 responded (56.2 %). The professional focus of the majority of respondents was critical care (106/249 (43 %)), pediatrics (59/249, (24 %)) or internal medicine (52/249 (21 %)) but none was blood banking. Nearly all respondents (251/263 (95 %)) reported to have access to ICU facilities within their institutions. Most respondents (219/270 (81 %)) reported that intensivists were the most physician group responsible for treatment decisions about critically ill SARI patients. While 125/165 respondents (76 %) reported that they conduct research in ICUs, and 80/161 (49.7 %) had been involved in the conduct of RCTs, including using a placebo comparison (60/161 (37 %)), only 49/226 (21 %) of respondents regularly participated in research networks. CONCLUSIONS: Our survey indicated that in the Kingdom of Saudi Arabia (KSA), ICUs are the most likely clinical locations for conducting a clinical trial of convalescent plasma therapy for MERS-CoV, and that most ICUs have experience with such research designs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12871-016-0198-x) contains supplementary material, which is available to authorized users.


title: RNA-mediated translation regulation in viral genomes: computational advances in the recognition of sequences and structures

text: RNA structures are widely distributed across all life forms. The global conformation of these structures is defined by a variety of constituent structural units such as helices, hairpin loops, kissing-loop motifs and pseudoknots, which often behave in a modular way. Their ubiquitous distribution is associated with a variety of functions in biological processes. The location of these structures in the genomes of RNA viruses is often coordinated with specific processes in the viral life cycle, where the presence of the structure acts as a checkpoint for deciding the eventual fate of the process. These structures have been found to adopt complex conformations and exert their effects by interacting with ribosomes, multiple host translation factors and small RNA molecules like miRNA. A number of such RNA structures have also been shown to regulate translation in viruses at the level of initiation, elongation or termination. The role of various computational studies in the preliminary identification of such sequences and/or structures and subsequent functional analysis has not been fully appreciated. This review aims to summarize the processes in which viral RNA structures have been found to play an active role in translational regulation, their global conformational features and the bioinformatics/computational tools available for the identification and prediction of these structures.


title: Validation of a short form Wisconsin Upper Respiratory Symptom Survey (WURSS-21)

text: BACKGROUND: The Wisconsin Upper Respiratory Symptom Survey (WURSS) is an illness-specific health-related quality-of-life questionnaire outcomes instrument. OBJECTIVES: Research questions were: 1) How well does the WURSS-21 assess the symptoms and functional impairments associated with common cold? 2) How well can this instrument measure change over time (responsiveness)? 3) What is the minimal important difference (MID) that can be detected by the WURSS-21? 4) What are the descriptive statistics for area under the time severity curve (AUC)? 5) What sample sizes would trials require to detect MID or AUC criteria? 6) What does factor analysis tell us about the underlying dimensional structure of the common cold? 7) How reliable are items, domains, and summary scores represented in WURSS? 8) For each of these considerations, how well does the WURSS-21 compare to the WURSS-44, Jackson, and SF-8? STUDY DESIGN AND SETTING: People with Jackson-defined colds were recruited from the community in and around Madison, Wisconsin. Participants were enrolled within 48 hours of first cold symptom and monitored for up to 14 days of illness. Half the sample filled out the WURSS-21 in the morning and the WURSS-44 in the evening, with the other half reversing the daily order. External comparators were the SF-8, a 24-hour recall general health measure yielding separate physical and mental health scores, and the eight-item Jackson cold index, which assesses symptoms, but not functional impairment or quality of life. RESULTS: In all, 230 participants were monitored for 2,457 person-days. Participants were aged 14 to 83 years (mean 34.1, SD 13.6), majority female (66.5%), mostly white (86.0%), and represented substantive education and income diversity. WURSS-21 items demonstrated similar performance when embedded within the WURSS-44 or in the stand-alone WURSS-21. Minimal important difference (MID) and Guyatt's responsiveness index were 10.3, 0.71 for the WURSS-21 and 18.5, 0.75 for the WURSS-44. Factorial analysis suggested an eight dimension structure for the WURSS-44 and a three dimension structure for the WURSS-21, with composite reliability coefficients ranging from 0.87 to 0.97, and Cronbach's alpha ranging from 0.76 to 0.96. Both WURSS versions correlated significantly with the Jackson scale (W-21 R = 0.85; W-44 R = 0.88), with the SF-8 physical health (W-21 R = -0.79; W-44 R = -0.80) and SF-8 mental health (W-21 R = -0.55; W-44 R = -0.60). CONCLUSION: The WURSS-44 and WURSS-21 perform well as illness-specific quality-of-life evaluative outcome instruments. Construct validity is supported by the data presented here. While the WURSS-44 covers more symptoms, the WURSS-21 exhibits similar performance in terms of reliability, responsiveness, importance-to-patients, and convergence with other measures.


title: A Beneficiary Role for Neuraminidase in Influenza Virus Penetration through the Respiratory Mucus

text: Swine influenza virus (SIV) has a strong tropism for pig respiratory mucosa, which consists of a mucus layer, epithelium, basement membrane and lamina propria. Sialic acids present on the epithelial surface have long been considered to be determinants of influenza virus tropism. However, mucus which is also rich in sialic acids may serve as the first barrier of selection. It was investigated how influenza virus interacts with the mucus to infect epithelial cells. Two techniques were applied to track SIV H1N1 in porcine mucus. The microscopic diffusion of SIV particles in the mucus was analyzed by single particle tracking (SPT), and the macroscopic penetration of SIV through mucus was studied by a virus in-capsule-mucus penetration system, followed by visualizing the translocation of the virions with time by immunofluorescence staining. Furthermore, the effects of neuraminidase on SIV getting through or binding to the mucus were studied by using zanamivir, a neuraminidase inhibitor (NAI), and Arthrobacter ureafaciens neuraminidase. The distribution of the diffusion coefficient shows that 70% of SIV particles were entrapped, while the rest diffused freely in the mucus. Additionally, SIV penetrated the porcine mucus with time, reaching a depth of 65 µm at 30 min post virus addition, 2 fold of that at 2 min. Both the microscopic diffusion and macroscopic penetration were largely diminished by NAI, while were clearly increased by the effect of exogenous neuraminidase. Moreover, the exogenous neuraminidase sufficiently prevented the binding of SIV to mucus which was reversely enhanced by effect of NAI. These findings clearly show that the neuraminidase helps SIV move through the mucus, which is important for the virus to reach and infect epithelial cells and eventually become shed into the lumen of the respiratory tract.


title: Establishment of canine and feline cells expressing canine signaling lymphocyte activation molecule for canine distemper virus study

text: Abstract Signaling lymphocyte activation molecule (SLAM) is one of the receptors for canine distemper virus (CDV). In this study, canine and feline cells expressing canine SLAM, designated A-72/cSLAM and CRFK/cSLAM, were established for the in vitro study of canine distemper. Recent CDV isolates, KDK-1 and 246, which belong to genotypes Asia/H1 and Asia/H2, respectively, rapidly grew and produced distinct syncytia in both the SLAM-expressing cells. The virus-neutralizing (VN) test was successfully performed using these cells, and the results indicated that sera from dogs experimentally infected with KDK-1 had higher VN titers for homologous strain KDK-1 than for heterologous strain 246 and the vaccine Onderstepoort. These newly established cells expressing canine SLAM would help virological and serological analyses of canine distemper.


title: Provide leadership to address economic impact of pandemic

text: “What should I be doing when I really don't know what will happen next? What can I learn?” Those are questions higher education leaders should be asking over the next few months about the impacts of the COVID‐19 pandemic, said Larenda Mielke, Vice President of Higher Education at Kaufman Hall.


title: Outbreak of Middle East respiratory syndrome coronavirus in Saudi Arabia: a retrospective study

text: BACKGROUND: The Middle East respiratory syndrome (MERS) is proposed to be a zoonotic disease. Dromedary camels have been implicated due to reports that some confirmed cases were exposed to camels. Risk factors for MERS coronavirus (MERS-CoV) infections in humans are incompletely understood. This study aimed to describe the demographic characteristics, mortality rate, clinical manifestations and comorbidities with confirmed cases of MERS-CoV. METHODS: Retrospective chart review were performed to identify all laboratory-confirmed cases of MERS-CoV in Saudi Arabia who reported to the Ministry of Health (MOH) of Saudi Arabia and WHO between April 23, 2014 and August 31, 2015. Patients’ charts were also reviewed for demographic information, mortality, comorbidities, clinical presentations, health care facility and presented with descriptive and comparative statistics using non parametric binomial test and Chi-square test. RESULTS: Confirmed cases of male patients (61.1%) exceeded those of female patients (38.9%). Infections among Saudi patients (62.6%) exceeded those among non-Saudi patients (37.4%; P = 0.001). The majority of the patients were aged 21–40 years (37.4%) or 41–60 years (35.8%); 43 (22.6%) were aged >61 years, and (8) 4.2% were aged 0–20 years. There was a difference in mortality between confirmed MERS-CoV cases (63.7% alive versus 36.3% dead cases, respectively). Furthermore, fever with cough and shortness of breath (SOB) (n = 39; 20.5%), fever with cough (n = 29; 15.3%), fever (n = 18; 9.5%), and fever with SOB (n = 13; 6.8%), were the most common clinical manifestations associated with confirmed MERS-CoV cases. CONCLUSION: MERS-CoV is considered an epidemic in Saudi Arabia. The results of the present study showed that the frequency of cases is higher among men than women, in Saudi patients than non-Saudi, and those between 21 to 60 years are most affected. Further studies are required to improve the surveillance associated with MERS-CoV to get definite and clear answers and better understanding of the MERS-CoV outbreak as well the source, and route of infection transmission in Saudi Arabia.


title: F-18-Fluorodeoxyglucose Positron Emission Tomography/CT Effectively Identifying Source of Infection in a Patient With Multiple Dialysis Arteriovenous Fistula Access Points

text: Radiologic imaging techniques, such as F-18-fluorodeoxyglucose positron emission tomography/computerized tomography (FDG PET/CT), provide diagnostic value in a variety of diseases. In cases of suspected infection, FDG PET/CT can find areas of fluorodeoxyglucose metabolism, correlating with local acute inflammation. The following case involves a man with end-stage renal disease (ESRD), who presented with symptoms of infection and positive blood cultures with high suspicion of arteriovenous fistula as the source of infection. The patient also had two central lines that could be a site of infection. Concerns for patient’s persistent positive blood cultures necessitated FDG PET/CT to confirm site of infection. Confirming active infection and the source of infection guides therapeutic measures and eliminates concern for other disease etiologies common in patients with ESRD.


title: Species-independent detection of RNA virus by representational difference analysis using non-ribosomal hexanucleotides for reverse transcription

text: A method for the isolation of genomic fragments of RNA virus based on cDNA representational difference analysis (cDNA RDA) was developed. cDNA RDA has been applied for the subtraction of poly(A)(+) RNAs but not for poly(A)(−) RNAs, such as RNA virus genomes, owing to the vast quantity of ribosomal RNAs. We constructed primers for inefficient reverse transcription of ribosomal sequences based on the distribution analysis of hexanucleotide patterns in ribosomal RNA. The analysis revealed that distributions of hexanucleotide patterns in ribosomal RNA and virus genome were different. We constructed 96 hexanucleotides (non-ribosomal hexanucleotides) and used them as mixed primers for reverse transcription of cDNA RDA. A synchronous analysis of hexanucleotide patterns in known viral sequences showed that all the known genomic-size viral sequences include non-ribosomal hexanucleotides. In a model experiment, when non-ribosomal hexanucleotides were used as primers, in vitro transcribed plasmid RNA was efficiently reverse transcribed when compared with ribosomal RNA of rat cells. Using non-ribosomal primers, the cDNA fragments of severe acute respiratory syndrome coronavirus and bovine parainfluenza virus 3 were efficiently amplified by subtracting the cDNA amplicons derived from uninfected cells from those that were derived from virus-infected cells. The results suggest that cDNA RDA with non-ribosomal primers can be used for species-independent detection of viruses, including new viruses.


Anti-Asian sentiment in the United States – COVID-19 and history


title: Antipsychotic treatment effects on cardiovascular, cancer, infection, and intentional self-harm as cause of death in patients with Alzheimer's dementia

text: Abstract Background Alzheimer's disease (AD), the most common disease causing dementia, is linked to increased mortality. However, the effect of antipsychotic use on specific causes of mortality has not yet been investigated thoroughly. Methods Utilizing the Danish nationwide registers, we defined a cohort of patients diagnosed with AD. Utilizing separate Cox regressions for specific causes of mortality, we investigated the effects of cumulative antipsychotic dosage after diagnosis and current antipsychotic exposure in the time period 2000–2011. Results In total, 45,894 patients were followed for 3,803,996 person-years. A total of 6129 cardiovascular related deaths, 2088 cancer related deaths, 1620 infection related deaths, and 28 intentional self-harm related deaths are presented. Current antipsychotic exposure increased mortality rate with HR between 1.92 and 2.31 for cardiovascular, cancer, and infection related death. Cumulative antipsychotic dosages were most commonly associated with increased rates of mortality for cardiovascular and infection as cause of death, whereas the associations were less clear with cancer and intentional self-harm as cause of death. Conclusions We showed that cumulative antipsychotic drug dosages increased mortality rates for cardiovascular and infection as cause of death. These findings highlight the need for further investigations of long-term effects of treatment and of possible sub-groups who could benefit from treatment.


Telemedicine for Inpatient Dermatology Consultations in Response to the COVID-19 Pandemic


title: A screening campaign in sea urchin egg homogenate as a platform for discovering modulators of NAADP-dependent Ca2+ signaling in human cells

text: Abstract The Ca2+ mobilizing second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) regulates intracellular trafficking events, including translocation of certain enveloped viruses through the endolysosomal system. Targeting NAADP-evoked Ca2+ signaling may therefore be an effective strategy for discovering novel antivirals as well as therapeutics for other disorders. To aid discovery of novel scaffolds that modulate NAADP-evoked Ca2+ signaling in human cells, we have investigated the potential of using the sea urchin egg homogenate system for a screening campaign. Known pharmacological inhibitors of NAADP-evoked Ca2+ release (but not cADPR- or IP3-evoked Ca2+ release) in this invertebrate system strongly correlated with inhibition of MERS-pseudovirus infectivity in a human cell line. A primary screen of 1534 compounds yielded eighteen ‘hits’ exhibiting >80% inhibition of NAADP-evoked Ca2+ release. A validation pipeline for these candidates yielded seven drugs that inhibited NAADP-evoked Ca2+ release without depleting acidic Ca2+ stores in a human cell line. These candidates displayed a similar penetrance of inhibition in both the sea urchin system and the human cell line, and the extent of inhibition of NAADP-evoked Ca2+ signals correlated well with observed inhibition of infectivity of a Middle East Respiratory syndrome coronavirus (MERS-CoV) pseudovirus. These experiments support the potential of this simple, homogenate system for screening campaigns to discover modulators of NAADP, cADPR and IP3-dependent Ca2+ signaling with potential therapeutic value.


title: Postgraduate Medical Training and COVID-19 Pandemic: Should We Stop, Freeze, or Continue?

text: Abstract While many countries in the world are going through a state of lockdown to limit the spread of coronavirus disease 2019 (COVID-19) [1], such a state may affect postgraduate medical training (PGMT) adversely in different aspects. These include a decreased number of clinical cases related to the specialty, staff shortage, cancelation of educational conferences, and difficulties conducting formal in-training and licensing examinations. Trainees, program directors, licensing bodies, and other stakeholders are in a difficult situation regarding what to do next. Such a situation raises several critical questions related to the training that we tried to address here.


title: Influenza-like Illness Incidence Is Not Reduced by Influenza Vaccination in a Cohort of Older Adults, Despite Effectively Reducing Laboratory-Confirmed Influenza Virus Infections

text: BACKGROUND: Data on the relative contribution of influenza virus and other respiratory pathogens to respiratory infections in community-dwelling older adults (≥60 years) are needed. METHODS: A prospective observational cohort study was performed in the Netherlands during 2 winters. Nasopharyngeal and oropharyngeal swabs were collected during influenza-like illness (ILI) episodes and from controls. Viruses and bacteria were identified by multiplex ligation–dependent probe amplification assay and conventional bacterial culture. RESULTS: The ILI incidence in the consecutive seasons was 7.2% and 11.6%, and influenza virus caused 18.9% and 34.2% of ILI episodes. Potential pathogen were detected in 80% of the ILI events with influenza virus, coronaviruses, rhinoviruses, human metapneumovirus, respiratory syncytial virus, parainfluenza viruses, and Haemophilus influenzae being the most common. Influenza vaccination reduced influenza virus infection by 73% (95% confidence interval [CI], 26%–90%) and 51% (95% CI, 7%–74%) in ILI patients. However, ILI incidence was similar between vaccinated (7.6% and 10.8%) and nonvaccinated (4.2% and 11.4%) participants in 2011–2012 and 2012–2013, respectively (P > .05). CONCLUSIONS: Influenza virus is a frequent pathogen in older adults with ILI. Vaccination reduces the number of influenza virus infections but not the overall number of ILI episodes: other pathogens fill the gap. We suggest the existence of a pool of individuals with high susceptibility to respiratory infections. CLINICAL TRIALS REGISTRATION: NTR3386.


title: Association of viral load with serum biomakers among COVID-19 cases

text: ABSTRACTS Since SARS-CoV-2 spreads rapidly around the world, data have been needed on the natural fluctuation of viral load and clinical indicators associated with it. We measured and compared viral loads of SARS-CoV-2 from pharyngeal swab, IgM anti-SARS-CoV-2, CRP and SAA from serum of 114 COVID-19 patients on admission. Positive rates of IgM anti-SARS-CoV-2, CRP and SAA were 80.7%, 36% and 75.4% respectively. Among IgM-positive patients, viral loads showed different trends among cases with different severity, While viral loads of IgM-negative patients tended to increase along with the time after onset. As the worsening of severity, the positive rates of CRP and SAA also showed trends of increase. Different CRP/SAA type showed associations with viral loads in patients in different severity and different time after onset. Combination of the IgM and CRP/SAA with time after onset and severity may give suggestions on the viral load and condition judgment of COVID-19 patients.


title: Psychology: a Discipline in Need of Reflective Foundations

text: Zagaria, Andó and Zennaro (2020) provide a useful analysis of the current state of affairs in the discipline of psychology. They conclude that psychology is in a messy and unproductive pre-pragmatic state and suggest that evolutionary psychology can provide a needed metatheoretical perspective to enable psychology to move forward as a science. In my commentary I move to another direction and suggest that psychology does not need more solid foundations, but rather foundations characterized by reflective stance towards its phenomena, theories, methods and data production processes. I suggest that this kind of stance would be in accordance with the process ontological perspective that allows focusing on meaningful human experience as central object of study for psychology, together with an idiographic approach to research. I thus suggest that psychology will endure only by turning its reflective gaze towards oneself, by thinking about its past, imagining its future and constructing novelty from the creative assemblage of the two.


title: Experimental infection of pigs with the porcine respiratory coronavirus (PRCV): measure of viral excretion

text: Abstract Twelve pigs were experimentally infected with a porcine respiratory coronavirus (PRCV) by the oronasal route. Viral excretion was measured daily by two means-deep nasal swabs and air samples obtained in a cyclone sampler. Clinical signs were very slight on infected pigs. Airborne virus could be recovered from day 1 to day 6 post-infection in the cyclone sampler as well as in petri dishes placed in the same loose-box. Viral titres obtained from nasal swabs were significantly correlated with those obtained from air samples. Different collection media were compared. The most efficient media for the collection of infectious viral particles contained a protective agent such as foetal calf serum.


title: Using the Pillars of Infection Prevention to Build an Effective Program for Reducing the Transmission of Emerging and Reemerging Infections

text: Preventing transmission of emerging infectious diseases remains a challenge for infection prevention and occupational safety programs. The recent Ebola and measles outbreaks highlight the need for pre-epidemic planning, early identification, and appropriate isolation of infected individuals and health care personnel protection. To optimally allocate limited infection control resources, careful consideration of major modes of transmission, the relative infectiousness of the agent, and severity of the pathogen-specific disease are considered. A framework to strategically approach pathogens proposed for health care settings includes generic principles (1) elimination of potential exposure, (2) implementation of administrative controls, (3) facilitation of engineering and environmental controls, and (4) protection of the health care worker and patient using hand hygiene and personal protective equipment. Additional considerations are pre-epidemic vaccination and incremental costs and benefits of infection prevention interventions. Here, major strategies for preventing health-care-associated transmissions are reviewed, including reducing exposure; vaccination; administrative, engineering, and environmental controls; and personal protective equipment. Examples from recent outbreaks are used to highlight key infection prevention aspects and controversies.


title: Untargeted liquid chromatography coupled with mass spectrometry reveals metabolic changes in nitrogen-deficient Isatis indigotica Fortune

text: Abstract Isatis indigotica Fortune is a popular herb in traditional Chinese medicine, and various types of metabolites are the basis for its pharmacological efficacy. The biosynthesis and accumulation of these metabolites are closely linked to nitrogen availability; the benefits of low nitrogen application on the environment and herb quality are increasingly prominent. To analyze metabolic changes in the leaves and roots of I.indigotica in nitrogen deficiency conditions, and to identify the pathways and metabolites induced by low nitrogen availability, we used untargeted liquid chromatography coupled with mass spectrometry (UHPLC-TripleTOF) to obtain metabolomics profiling of I.indigotica under two N-deficiency treatments (0 kg/hm2; 337.5 kg/hm2) and normal nitrogen treatment (675 kg/hm2). A total of 447 metabolites were annotated. Principal component analysis separated the three nitrogen treatments. A greater diversity of metabolites was observed in roots than in leaves under N-deficiency treatments, suggesting that roots have a more important function in low N tolerance. Differential metabolites were mainly enriched in purine metabolism, phenylpropanoid biosynthesis, the shikimate pathway, tryptophan metabolism, and flavonoid biosynthesis that notably induced only in leaves in low nitrogen stress. Moderate N-deficiency benefits carbohydrate accumulation, whereas accumulation of most amino acids decreases. Uniquely, L-tryptophan was maintained at a high concentration in N-deficiency conditions. Low nitrogen stress induced the accumulation of some specialized metabolites (matairesinol, dictamnine, 5-hydroxyindoleacetate (serotonin) in roots and vitexin, xanthohumol, sinapyl alcohol in leaves). N-deficiency also increased the accumulation of adenosine and quality indicators of I.indigotica (indirubin-indigo, epigoitrin and anthranilic acid) in a certain degree. Our findings showed that nitrogen deficiency modified roots and leaves conditions of I.indigotica, affecting both the primary and secondary metabolism. Moderate nitrogen reduction was beneficial to the accumulation of active ingredients. Our methods and analysis are expected to provide an insight regarding the diversity of metabolites and regulation of their synthesis in low nitrogen application, and better investigate the nitrogen deficiency effect on I.indigotica.


title: Determinants of the p28 Cleavage Site Recognized by the First Papain-like Cysteine Proteinase of Murine Coronavirus

text: Abstract The murine coronavirus polymerase gene is 22 kb in length with the potential to encode a polyprotein of approximately 750 kDa. The polyprotein has been proposed to encode three proteinase domains which are responsible for the processing of the polyprotein into mature proteins. The proteolytic activity of the first proteinase domain has been characterized and resembles the papain family of cysteine proteinases. This proteinase domain acts autoproteolytically to cleave the amino terminal portion of the polymerase polyprotein, releasing a 28-kDa protein designated p28. To identify the cleavage site of this papain-like cysteine proteinase, we isolated the peptide adjacent to p28 and determined the amino terminus sequence by Edman degradation reaction. We report that proteolysis occurs between the Gly-247 and Val-248 dipeptide bond. To determine the role of the amino acid residues surrounding the cleavage site, we introduced a total of 42 site-specific mutations at the residues spanning the P5 to P3′ positions and assessed the effects of the mutations on the processing of p28 in an in vitro transcription and translation system. The substitutions of Gly-247 at the P1 position or Arg-246 at the P2 position resulted in a dramatic decrease of proteolytic activity, and the mutations of Arg-243 at P5 position also led to considerable reduction in p28 cleavage. In contrast, the substitutions of amino acids Gly-244 (P4), Tyr-245 (P3), Val-248 (P1′), Lys-249 (P2′), and Pro-250 (P3′) had little or no effect on the amount of p26 that was released. This work has identified Gly-247-Val-248 as the cleavage site for the release of p28, the amino-terminal protein of the murine coronavirus polymerase polyprotein. Additionally, we conclude that the Gly-247 and Arg-246 are the major determinants for the cleavage site recognition by the first papain-like cysteine proteinase of murine coronavirus.


title: Characterization of 2009 H1N1 pandemic influenza in a population of Dutch children with influenza‐like signs and symptoms

text: Aim: To determine causative respiratory pathogens and describe epidemiological and clinical characteristics in a paediatric population with influenza‐like illness during the 2009 H1N1‐pandemic. Methods: Observational study of 412 children visiting an outpatient clinic of a Dutch teaching hospital. Results: From August to December 2009, 412 children were tested at the clinic; 32% proved H1N1‐positive, confirmed by reverse‐transcriptase‐polymerase‐chain‐reaction (RT‐PCR). Pathogens were detected in 65% of samples. Influenza A(H1N1) (n = 132), human rhinovirus (n = 55), respiratory syncytial virus (n = 45) and adenovirus (n = 34) were mostly identified. Co‐infections were seen in 34 children (8.3%). Mean age was 6.8 and 4.2 years in H1N1‐positive and H1N1‐negative cases, respectively (p < 0.01). H1N1‐positive outpatient children reported fever, cough and rhinorrhoea more frequently than their H1N1‐negative counterparts. Of 72 hospitalized children, 31% proved H1N1‐positive; all showed a relatively mild clinical illness. None of the children had been admitted to an intensive care unit or died. Oseltamivir treatment was initiated in 72 children and discontinued in 42 (63%) when RT‐PCR results turned negative. Conclusion: The 2009 H1N1‐pandemic showed a mild clinical course in a Dutch paediatric outpatient clinic population. Respiratory pathogens were detected in the majority of children with influenza‐like illness and influenza A(H1N1) virus was identified in one‐third. Testing symptomatic children during an influenza pandemic has effectively limited the use of oseltamivir.


title: SARS-COV2 INFECTION AND LUNG CANCER PATIENTS: the potential role of IL17 target therapy

text: Abstract The coronavirus disease 2019 (Covid-19) outbreak is evolving rapidly worldwide. The Lung is the target organ of the primary infection and patient whit lung cancer seems to have a poor prognosis. This is the first reported investigation on a possible role of IL 17 target therapy in Lung Cancer patients with concomitant Sars-CoV2 infection.


title: Psoriasis, biological drugs and Coronavirus Disease 2019: Real life experience of two Italian provinces

text: On January 30, 2020, World Health Organization (WHO) stated that a new coronavirus disease outbreak [COronaVIrus Disease - 19 (COVID-19)] was an international public health emergency. Many news, often fake ones, about the derived pandemic rapidly spread along the media, thus leading many dermatological patients to identify as “risk category” and sometimes discontinue treatments by themselves. The Dermatology Units in Grosseto and Pordenone simultaneously carried out a data collection by remote-conducted visits, evaluating the incidence of COVID-19 in psoriatic patients. Only 1 patient (close contact of a case) as part of the psoriasis analyzed group was tested and turned out to be positive for SARS-CoV-2, developing no symptoms during the observation period. The collected information may suggest that psoriasis, biotechnologically treated or not, cannot promote or aggravate the clinical trend of the SARS-CoV-2 infection, hence stopping systemic therapy in negative or clinically free SARS-CoV-2 patients is not recommended in general.


title: High Level of Food Insecurity among Families with Children Seeking Routine Care at Federally Qualified Health Centers during the COVID-19 Pandemic

text: Objective To assess food insecurity during pediatric visits to federally qualified health centers (FQHC) during the COVID-19 pandemic. Study design Interviews using the validated American Academy of Pediatrics 2-question food insecurity screen were performed with 200 consecutive families presenting for pediatric care to two FQHC in Central Texas from April 14 to May 20, 2020. Brief qualitative interviews were conducted to determine whether families found a worsening of food insecurity during the pandemic. Results Overall, 47% of families had a positive food insecurity screen. Over 90% of these were worrying about food running out whereas about 60% were positive for the question related to food not lasting. Among food insecurity families, 94% indicated this had begun or worsened during the pandemic. Of the 115 families volunteering information about employment, 46% reported job loss during this time period. Both ethnicity (p < 0.001) and WIC participation (p = 0.03) were associated with greater levels of food insecurity. Among primarily Spanish speaking families participating in the WIC program, 64% reported food insecurity. Conclusions Approximately one-half of families receiving routine pediatric care at a FQHC during the COVID-19 pandemic reported food insecurity and this was associated with loss of jobs during the pandemic. Participation in the WIC program was not protective against food insecurity. Increased frequency of food insecurity was detected in Hispanic and Spanish speaking families. Screening of families at an FQHC should be strongly considered as part of routine pediatric care. Knowledge of community resources is important for providers to share with patients.


title: SARS-CoV-2 and viral sepsis: observations and hypotheses

text: Summary Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have tried every effort to understand the disease, and a brief portrait of its clinical features have been identified. In clinical practice, we noticed that many severe or critically ill COVID-19 patients developed typical clinical manifestations of shock, including cold extremities and weak peripheral pulses, even in the absence of overt hypotension. Understanding the mechanism of viral sepsis in COVID-19 is warranted for exploring better clinical care for these patients. With evidence collected from autopsy studies on COVID-19 and basic science research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, we have put forward several hypotheses about SARS-CoV-2 pathogenesis after multiple rounds of discussion among basic science researchers, pathologists, and clinicians working on COVID-19. We hypothesise that a process called viral sepsis is crucial to the disease mechanism of COVID-19. Although these ideas might be proven imperfect or even wrong later, we believe they can provide inputs and guide directions for basic research at this moment.


title: Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi-Challenge

text: Dogs represent the most important domestic reservoir of L. chagasi (syn. L. infantum). A vaccine against canine visceral leishmaniasis (CVL) would be an important tool for decreasing the anxiety related to possible L. chagasi infection and for controlling human visceral leishmaniasis (VL). Because the sand fly salivary proteins are potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in past decades. We investigated the immunogenicity of the “LbSapSal” vaccine (L. braziliensis antigens, saponin as adjuvant, and Lutzomyia longipalpis salivary gland extract) in dogs at baseline (T(0)), during the post-vaccination protocol (T(3rd)) and after early (T(90)) and late (T(885)) times following L. chagasi-challenge. Our major data indicated that immunization with “LbSapSal” is able to induce biomarkers characterized by enhanced amounts of type I (tumor necrosis factor [TNF]-α, interleukin [IL]-12, interferon [IFN]-γ) cytokines and reduction in type II cytokines (IL-4 and TGF-β), even after experimental challenge. The establishment of a prominent pro-inflammatory immune response after “LbSapSal” immunization supported the increased levels of nitric oxide production, favoring a reduction in spleen parasitism (78.9%) and indicating long-lasting protection against L. chagasi infection. In conclusion, these results confirmed the hypothesis that the “LbSapSal” vaccination is a potential tool to control the Leishmania chagasi infection.


title: Rhinovirus Infections in Hematopoietic Stem Cell Transplant Recipients with Pneumonia

text: Little is known about the impact of human rhinovirus (HRV) and coronavirus infections in hematopoietic stem cell transplant (HSCT) recipients. We tested bronchoalveolar lavage (BAL) samples obtained from HSCT recipients with acute pulmonary infiltrates for HRV (n = 122) and coronavirus (n = 46) by reverse-transcriptase polymerase chain reaction. HRV RNA was detected in 6 (8%) of 77 patients, and coronavirus RNA was detected in 0 of 46 of BAL samples from HSCT recipients. The fatality rate in HRV-infected patients was high (83%), but all patients had significant coinfections, and the overall mortality rate was not different from that of patients who were negative for HRV in BAL samples. These results suggest that HRV may be a cause of lower respiratory tract infections in HSCT recipients and that its detection in BAL samples is associated with frequent copathogens. Whether the poor prognosis is due to HRV or the copathogen is not clear.


title: Models of Lung Disease: Microscopy and Structural Methods Joan Gil Mod

text: Unknown


title: Inhibitory Effect of Matrine on Blood-Brain Barrier Disruption for the Treatment of Experimental Autoimmune Encephalomyelitis

text: Dysfunction of the blood-brain barrier (BBB) is a primary characteristic of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to suppress clinical EAE and CNS inflammation. However, whether this effect of MAT is through protecting the integrity and function of the BBB is not known. In the present study, we show that MAT treatment had a therapeutic effect comparable to dexamethasone (DEX) in EAE rats, with reduced Evans Blue extravasation, increased expression of collagen IV, the major component of the basement membrane, and the structure of tight junction (TJ) adaptor protein Zonula occludens-1 (ZO-1). Furthermore, MAT treatment attenuated expression of matrix metalloproteinase-9 and -2 (MMP-9/-2), while it increased the expression of tissue inhibitors of metalloproteinase-1 and -2 (TIMP-1/-2). Our findings demonstrate that MAT reduces BBB leakage by strengthening basement membrane, inhibiting activities of MMP-2 and -9, and upregulating their inhibitors. Taken together, our results identify a novel mechanism underlying the effect of MAT, a natural compound that could be a novel therapy for MS.


title: Neonatal Immune Development in the Calf and Its Impact on Vaccine Response

text: In this article we cover the immunologic response as it develops, the components of passive immunity, and the immune response of young calves. We discuss interference from maternal immunity in the development of specific immunity and vaccine strategies for developing protection against pathogens in calves.


title: Microbial and fungal protease inhibitors—current and potential applications

text: Proteolytic enzymes play essential metabolic and regulatory functions in many biological processes and also offer a wide range of biotechnological applications. Because of their essential roles, their proteolytic activity needs to be tightly regulated. Therefore, small molecules and proteins that inhibit proteases can be versatile tools in the fields of medicine, agriculture and biotechnology. In medicine, protease inhibitors can be used as diagnostic or therapeutic agents for viral, bacterial, fungal and parasitic diseases as well as for treating cancer and immunological, neurodegenerative and cardiovascular diseases. They can be involved in crop protection against plant pathogens and herbivorous pests as well as against abiotic stress such as drought. Furthermore, protease inhibitors are indispensable in protein purification procedures to prevent undesired proteolysis during heterologous expression or protein extraction. They are also valuable tools for simple and effective purification of proteases, using affinity chromatography. Because there are such a large number and diversity of proteases in prokaryotes, yeasts, filamentous fungi and mushrooms, we can expect them to be a rich source of protease inhibitors as well.


title: The “sweet” side of a long pentraxin: how glycosylation affects PTX3 functions in innate immunity and inflammation

text: Innate immunity represents the first line of defense against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognize pathogen-associated molecular patterns and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a non-redundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the crossroad between innate immunity, inflammation, and female fertility. The human PTX3 protein contains a single N-glycosylation site that is fully occupied by complex type oligosaccharides, mainly fucosylated and sialylated biantennary glycans. Glycosylation has been implicated in a number of PTX3 activities, including neutralization of influenza viruses, modulation of the complement system, and attenuation of leukocyte recruitment. Therefore, this post translational modification might act as a fine tuner of PTX3 functions in native immunity and inflammation. Here we review the studies on PTX3, with emphasis on the glycan-dependent mechanisms underlying pathogen recognition and crosstalk with other components of the innate immune system.


title: Chapter 12 Viral Disease

text: Publisher Summary This chapter discusses the infections caused by DNA viruses and also RNA viruses. The chapter focuses on the detection, diagnosis, risk assessment, and decision-making regarding viral infections. Several infections caused by DNA viruses are parvoviruses, rat cytomegalovirus, poxviruses, adenovirus, and papovavirus. Several RNA viruses and infections caused by these viruses are coronaviruses, paramyxoviruses, rotavirus and reovirus, and picornaviruses. Monitoring for viral infections should cover at least three venues: animals in established breeding and experimental colonies, animals held in entry quarantine, and animal tissues and products destined for in vivo use. For established colonies, monitoring should be tailored to local conditions. Effective monitoring should encompass sampling on a pre-arranged schedule, which can be intensified if evidence or suspicion of viral infection emerges. Because viral infections of rats can spread insidiously, early detection and epidemiologic “staging” should employ a detection matrix that includes clinical observation, appropriate sampling, and sensitive and specific diagnostic testing.


title: Potential Output, EU Fiscal Surveillance and the COVID-19 Shock

text: This paper discusses how the technical foundations of the EU’s fiscal rules constrain the fiscal space in EU countries in the context of the COVID-19 pandemic. We review the evidence on how estimates of potential output, which are at the heart of essential control indicators in EU fiscal surveillance, were revised in the ten years running up to the COVID-19 pandemic, and how these revisions affected the fiscal stance of EU countries. We provide first evidence for downward revisions in the European Commission’s potential output estimates against the background of the COVID-19 shock across the EU27 countries, and we assess the potential consequences in terms of fiscal space. According to our results, one additional percentage point in predicted losses of actual output is associated with a loss in potential output of about 0.6 percentage points. Given the importance of model-based estimates in the EU’s fiscal rules, avoiding pro-cyclical fiscal tightening will require that policymakers’ hands are not tied by overly pessimistic views on the development of potential output.


title: The spray-drying process is sufficient to inactivate infectious porcine epidemic diarrhea virus in plasma

text: Abstract Porcine epidemic diarrhea virus (PEDV) is considered an emergent pathogen associated with high economic losses in many pig rearing areas. Recently it has been suggested that PEDV could be transmitted to naïve pig populations through inclusion of spray-dried porcine plasma (SDPP) into the nursery diet which led to a ban of SDPP in several areas in North America and Europe. To determine the effect of spray-drying on PEDV infectivity, 3-week-old pigs were intragastrically inoculated with (1) raw porcine plasma spiked with PEDV (RAW-PEDV-CONTROL), (2) porcine plasma spiked with PEDV and then spray dried (SD-PEDV-CONTROL), (3) raw plasma from PEDV infected pigs (RAW-SICK), (4) spray-dried plasma from PEDV infected pigs (SD-SICK), or (5) spray-dried plasma from PEDV negative pigs (SD-NEG-CONTROL). For the spray-drying process, a tabletop spray-dryer with industry-like settings for inlet and outlet temperatures was used. In the RAW-PEDV-CONTROL group, PEDV RNA was present in feces at day post infection (dpi) 3 and the pigs seroconverted by dpi 14. In contrast, PEDV RNA in feces was not detected in any of the pigs in the other groups including the SD-PEDV-CONTROL group and none of the pigs had seroconverted by termination of the project at dpi 28. This work provides direct evidence that the experimental spray-drying process used in this study was effective in inactivating infectious PEDV in the plasma. Additionally, plasma collected from PEDV infected pigs at peak disease did not contain infectious PEDV. These findings suggest that the risk for PEDV transmission through commercially produced SDPP is minimal.


title: A look at the ASEAN-NDI: building a regional health R&D innovation network

text: Globally, there are growing efforts to address diseases through the advancement in health research and development (R&D), strengthening of regional cooperation in science and technology (particularly on product discovery and development), and implementation of the World Health Assembly Resolution 61.21 (WHA61.21) on the Global Strategy and Plan of Action on Public Health, Innovation, and Intellectual Property (GSPA-PHI). As such, the Association of Southeast Asian Nations (ASEAN) is responding to this through the establishment of the ASEAN-Network for Drugs, Diagnostics, Vaccines, and Traditional Medicines Innovation (ASEAN-NDI). This is important in the ASEAN considering that infectious tropical diseases remain prevalent, emerging, and reemerging in the region. This paper looks into the evolution of the ASEAN-NDI from its inception in 2009, to how it is at present, and its plans to mitigate public health problems regionally and even globally.


title: Chapter 4 Bioactivity and Synthesis of Diarylheptanoids From Alpinia officinarum

text: Abstract Many diarylheptanoids were isolated from the galangal (rhizome of Alpinia officinarum). We are reported the antitumor-promoting, antiinflammatory, cytotoxic, antiinfluenza virus, and antiherpes simplex-1 virus activities of diarylheptanoids. These components in our dietary and herbal supplements are considered to be relatively nontoxic to human. In addition, we synthesized the new compounds. In this review, we discuss the antitumor-promoting, antiinflammatory, cytotoxic, antimicrobial, antiinfluenza, and antiherpes simplex-1 virus activities of diarylheptanoids isolated from galangal resulting from our own and other research groups' investigation.


title: Coronavirus Disease 2019: A Comprehensive Review of Etiology, Pathogenesis, Diagnosis, and Ongoing Clinical Trials

text: Coronavirus disease 2019 (COVID-19) is an acute respiratory viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease outbreak started in China in late December 2019 and quickly spread to the rest of the world, resulting in a pandemic. The incidence of cases is increasing every day, affecting millions of people around the globe and resulting in a public health emergency. Furthermore, disease management has been challenging for the clinicians and other medical personnel in terms of treatment options and availability of personal protective equipment. The off-label use of drugs such as hydroxychloroquine and emergency use authorization of remdesivir can hopefully help the clinicians while treating critically ill patients. The use of convalescent serum has also shown some interim benefit until a definitive treatment and preventive options are uncovered, such as vaccines and other effective treatment regimens.


title: Why is SARS-CoV-2 infection more severe in obese men? The gut lymphatics - lung axis hypothesis

text: Consistent observations report increased severity of SARS-CoV-2 infection in overweight men with cardiovascular factors. As the visceral fat possesses an intense immune activity, is involved in metabolic syndrome and is at the crossroad between the intestines, the systemic circulation and the lung, we hypothesized that it plays a major role in severe forms of SARS-CoV-2 infection. SARS-CoV2 presents the ability to infect epithelial cells of the respiratory tract as well as the intestinal tract. Several factors may increase intestinal permeability including, direct enterocyte damage by SARS-CoV2, systemic inflammatory response syndrome (SIRS) and epithelial ischemia secondary to SARS-CoV2- associated endothelial dysfunction. This increase permeability further leads to translocation of microbial components such as MAMPS (microbial-associated molecular pattern), triggering an inflammatory immune response by TLR-expressing cells of the mesentery fat (mostly macrophages and adipocytes). The pro-inflammatory cytokines produced by the mesentery fat mediates systemic inflammation and aggravate acute respiratory distress syndrome (ARDS) through the mesenteric lymph drainage.


title: Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study

text: INTRODUCTION: Accurate and timely diagnosis of community-acquired bacterial infections in patients with systemic inflammation remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival. We therefore compared the diagnostic characteristics of novel and routinely used biomarkers of sepsis alone and in combination. METHODS: This prospective cohort study included patients with systemic inflammatory response syndrome who were suspected of having community-acquired infections. It was conducted in a medical emergency department and department of infectious diseases at a university hospital. A multiplex immunoassay measuring soluble urokinase-type plasminogen activator (suPAR) and soluble triggering receptor expressed on myeloid cells (sTREM)-1 and macrophage migration inhibitory factor (MIF) was used in parallel with standard measurements of C-reactive protein (CRP), procalcitonin (PCT), and neutrophils. Two composite markers were constructed – one including a linear combination of the three best performing markers and another including all six – and the area under the receiver operating characteristic curve (AUC) was used to compare their performance and those of the individual markers. RESULTS: A total of 151 patients were eligible for analysis. Of these, 96 had bacterial infections. The AUCs for detection of a bacterial cause of inflammation were 0.50 (95% confidence interval [CI] 0.40 to 0.60) for suPAR, 0.61 (95% CI 0.52 to 0.71) for sTREM-1, 0.63 (95% CI 0.53 to 0.72) for MIF, 0.72 (95% CI 0.63 to 0.79) for PCT, 0.74 (95% CI 0.66 to 0.81) for neutrophil count, 0.81 (95% CI 0.73 to 0.86) for CRP, 0.84 (95% CI 0.71 to 0.91) for the composite three-marker test, and 0.88 (95% CI 0.81 to 0.92) for the composite six-marker test. The AUC of the six-marker test was significantly greater than that of the single markers. CONCLUSION: Combining information from several markers improves diagnostic accuracy in detecting bacterial versus nonbacterial causes of inflammation. Measurements of suPAR, sTREM-1 and MIF had limited value as single markers, whereas PCT and CRP exhibited acceptable diagnostic characteristics. TRIAL REGISTRATION: NCT 00389337


title: Community Pharmacists: On the frontline of health service against COVID-19 in LMICs

text: Abstract The COVID-19 outbreak is a global public health crisis which has affected healthcare practice across professions. In the context of this pandemic, there is a need to highlight the roles and responsibilities of pharmacists. Community pharmacists are the most accessible healthcare professionals to the general public and have a lot to offer amid the COVID-19 response. This have led to significant changes in the health systems of many countries. This article seeks to highlight additional roles and activities relating to the public health response that can be undertaken by community pharmacists that could help to reduce pressure on general practice and other areas of the health service.


title: Isolation and molecular characterization of bovine enteroviruses in Egypt

text: Abstract Enteroviruses belong to the Picornaviridae family and infect a wide range of mammals including cattle. Bovine enterovirus (BEV) has recently been reclassified into E and F serotypes. BEV was first isolated in Egypt in 1966 although it has been known in other countries since the 1950s. In this study, BEV-F2 was isolated from calves with severe diarrhea and the isolated viruses were subjected to molecular characterization. Illumina sequencing of one of the isolates revealed the presence of a complete BEV-F genome sequence. The phylogenetic analysis revealed nucleotide substitutions along the genome in comparison with other known strains of BEV-F (HQ663846, AY508697 and DQ092795). Two primer sets were designed from the 3D and 5′NTR regions and used for the examination of the remaining isolates, which were confirmed to be of the BEV-F2 serotype. The availability of the complete genome sequence of this virus adds to the sequence database of the members of Picornaviridae and should be useful in future molecular studies of BEV.


title: Chitosans for delivery of nucleic acids

text: Abstract Alternatives to efficient viral vectors in gene therapy are desired because of their poor safety profiles. Chitosan is a promising non-viral nucleotide delivery vector because of its biocompatibility, biodegradability, low immunogenicity and ease of manufacturing. Since the transfection efficiency of chitosan polyplexes is relatively low compared to viral counterparts, there is an impetus to gain a better understanding of the structure–performance relationship. Recent progress in preparation and characterisation has enabled coupling analysis of chitosans structural parameters that has led to increased TE by tailoring of chitosan's structure. In this review, we summarize the recent advances that have lead to a more rational design of chitosan polyplexes. We present an integrated review of all major areas of chitosan-based transfection, including preparation, chitosan and polyplexes physicochemical characterisation, in vitro and in vivo assessment. In each, we present the obstacles to efficient transfection and the strategies adopted over time to surmount these impediments.


title: Two novel neutralizing antigenic epitopes of the s1 subunit protein of a QX-like avian infectious bronchitis virus strain Sczy3 as revealed using a phage display peptide library

text: Abstract The spike (S) protein of the infectious bronchitis virus (IBV) plays a central role in the pathogenicity, the immune antibody production, serotype and the tissue tropism. In this study, we generate 11 monoclonal antibodies (mAbs) against S1 subunit of IBV Sczy3 strain, and two mAbs 1D5 and 6A12 were positive in indirect ELISA against both His-S1 protein and the purified whole viral antigen. MAb 6A12 and 1D5 could recognized by other 10 IBV strains (IBVs) from five different genotypes, except that 1D5 had a relatively low reaction with two of the 10 tested IBVs. End-point neutralizing assay performed in chicken embro kidney (CEK) cells revealed that the neutralization titer of 6A12 and 1D5 against Sczy3 reached 1:44.7 and 1:40.6, respectively. After screening a phage display peptide library and peptide scanning, we identified two linear B-cell epitopes that were recognized by the mAbs 1D5 and 6A12, which corresponded to the amino acid sequences 87PPQGMAW93 and 412IQTRTEP418, respectively, in the IBV S1 subunit. Sequences comparison revealed that epitope 412IQTRTEP418 was conserved among IBVs, while the epitope 87PPQGMAW93 was relatively variable among IBVs. The novel mAbs and the epitopes identified will be useful for developing diagnostic assays for IBV infections.


title: Asymmetric evolution in viral overlapping genes is a source of selective protein adaptation

text: Abstract Overlapping genes represent an intriguing puzzle, as they encode two proteins whose ability to evolve is constrained by each other. Overlapping genes can undergo “symmetric evolution” (similar selection pressures on the two proteins) or “asymmetric evolution” (significantly different selection pressures on the two proteins). By sequence analysis of 75 pairs of homologous viral overlapping genes, I evaluated their accordance with one or the other model. Analysis of nucleotide and amino acid sequences revealed that half of overlaps undergo asymmetric evolution, as the protein from one frame shows a number of substitutions significantly higher than that of the protein from the other frame. Interestingly, the most variable protein (often known to interact with the host proteins) appeared to be encoded by the de novo frame in all cases examined. These findings suggest that overlapping genes, besides to increase the coding ability of viruses, are also a source of selective protein adaptation.


title: A transcutaneous vaccination system using a hydrogel patch for viral and bacterial infection

text: Abstract One of the most important anthropic missions is preventing the global spread of infectious diseases. Vaccination is the only available preventive treatment for infectious diseases, but the availability of vaccines in developing countries is not adequate. We report a simple, easy-to-use, noninvasive hydrogel patch transcutaneous vaccination system. Antigen (Ag)-specific IgG production was induced by applying an Ag-immersed patch to non-pretreated mouse auricle or hairless rat back skin. Immunofluorescence histochemical analysis revealed that Langerhans cells resident in the epidermal layer captured the antigenic proteins delivered by the hydrogel patch, which promoted the penetration of antigenic proteins through the stratum corneum, and that Ag-capturing Langerhans cells migrated into draining lymph nodes. Humoral immunity elicited by our transcutaneous vaccination system demonstrated neutralizing activity in both adenoviral infection and passive-challenge tetanus toxin experiments. The use of this hydrogel patch transcutaneous vaccination system will facilitate the global distribution of effective and convenient vaccines.


title: Symmetric dimeric adamantanes for exploring the structure of two viroporins: influenza virus M2 and hepatitis C virus p7

text: BACKGROUND: Adamantane-based compounds have been identified to interfere with the ion-channel activity of viroporins and thereby inhibit viral infection. To better understand the difference in the inhibition mechanism of viroporins, we synthesized symmetric dimeric adamantane analogs of various alkyl-spacer lengths. METHODS: Symmetric dimeric adamantane derivatives were synthesized where two amantadine or rimantadine molecules were linked by various alkyl-spacers. The inhibitory activity of the compounds was studied on two viroporins: the influenza virus M2 protein, expressed in Xenopus oocytes, using the two-electrode voltage-clamp technique, and the hepatitis C virus (HCV) p7 channels for five different genotypes (1a, 1b, 2a, 3a, and 4a) expressed in HEK293 cells using whole-cell patch-clamp recording techniques. RESULTS: Upon testing on M2 protein, dimeric compounds showed significantly lower inhibitory activity relative to the monomeric amantadine. The lack of channel blockage of the dimeric amantadine and rimantadine analogs against M2 wild type and M2-S31N mutant was consistent with previously proposed drug-binding mechanisms and further confirmed that the pore-binding model is the pharmacologically relevant drug-binding model. On the other hand, these dimers showed similar potency to their respective monomeric analogs when tested on p7 protein in HCV genotypes 1a, 1b, and 4a while being 700-fold and 150-fold more potent than amantadine in genotypes 2a and 3a, respectively. An amino group appears to be important for inhibiting the ion-channel activity of p7 protein in genotype 2a, while its importance was minimal in all other genotypes. CONCLUSION: Symmetric dimeric adamantanes can be considered a prospective class of p7 inhibitors that are able to address the differences in adamantane sensitivity among the various genotypes of HCV.


BREAST CANCER SCREENING OF MUTATION CARRIERS IN THE ERA OF COVID‐19 PANDEMIC


Has osteopathy a role to play in treatment of flu?


title: Urban Air Pollution May Enhance COVID-19 Case-Fatality and Mortality Rates in the United States

text: BACKGROUND: The novel human coronavirus disease 2019 (COVID-19) pandemic has claimed more than 240,000 lives worldwide, causing tremendous public health, social, and economic damages. While the risk factors of COVID-19 are still under investigation, environmental factors, such as urban air pollution, may play an important role in increasing population susceptibility to COVID-19 pathogenesis. METHODS: We conducted a cross-sectional nationwide study using zero-inflated negative binomial models to estimate the association between long-term (2010–2016) county-level exposures to NO(2), PM(2.5) and O(3) and county-level COVID-19 case-fatality and mortality rates in the US. We used both single and multipollutant models and controlled for spatial trends and a comprehensive set of potential confounders, including state-level test positive rate, county-level healthcare capacity, phase-of-epidemic, population mobility, sociodemographic, socioeconomic status, behavior risk factors, and meteorological factors. RESULTS: 1,027,799 COVID-19 cases and 58,489 deaths were reported in 3,122 US counties from January 22, 2020 to April 29, 2020, with an overall observed case-fatality rate of 5.8%. Spatial variations were observed for both COVID-19 death outcomes and long-term ambient air pollutant levels. County-level average NO(2) concentrations were positively associated with both COVID-19 case-fatality rate and mortality rate in single-, bi-, and tri-pollutant models (p-values<0.05). Per inter-quartile range (IQR) increase in NO(2) (4.6 ppb), COVID-19 case-fatality rate and mortality rate were associated with an increase of 7.1% (95% CI 1.2% to 13.4%) and 11.2% (95% CI 3.4% to 19.5%), respectively. We did not observe significant associations between long-term exposures to PM(2.5) or O(3) and COVID-19 death outcomes (p-values>0.05), although per IQR increase in PM(2.5) (3.4 ug/m(3)) was marginally associated with 10.8% (95% CI: −1.1% to 24.1%) increase in COVID-19 mortality rate. DISCUSSIONS AND CONCLUSIONS: Long-term exposure to NO(2), which largely arises from urban combustion sources such as traffic, may enhance susceptibility to severe COVID-19 outcomes, independent of long-term PM(2.5) and O(3) exposure. The results support targeted public health actions to protect residents from COVID-19 in heavily polluted regions with historically high NO(2) levels. Moreover, continuation of current efforts to lower traffic emissions and ambient air pollution levels may be an important component of reducing population-level risk of COVID-19 deaths.


title: Clinical characteristics and prognostic factors in COVID‐19 patients aged ≥80 years

text: AIM: The aim of the present study was to describe the clinical presentation of patients aged ≥80 years with coronavirus disease 2019 (COVID‐19), and provide insights regarding the prognostic factors and the risk stratification in this population. METHODS: This was a single‐center, retrospective, observational study, carried out in a referral center for COVID‐19 in central Italy. We reviewed the clinical records of patients consecutively admitted for confirmed COVID‐19 over a 1‐month period (1–31 March 2020). We excluded asymptomatic discharged patients. We identified risk factors for death, by a uni‐ and multivariate Cox regression analysis. To improve model fitting and hazard estimation, continuous parameters where dichotomized by using Youden’s index. RESULTS: Overall, 69 patients, aged 80–98 years, met the inclusion criteria and were included in the study cohort. The median age was 84 years (82–89 years is interquartile range); 37 patients (53.6%) were men. Globally, 14 patients (20.3%) presented a mild, 30 (43.5%) a severe and 25 (36.2%) a critical COVID‐19 disease. A total of 23 (33.3%) patients had died at 30 days’ follow up. Multivariate Cox regression analysis showed that severe dementia, pO(2) ≤90 at admission and lactate dehydrogenase >464 U/L were independent risk factors for death. CONCLUSIONS: The present data suggest that risk of death could be not age dependent in patients aged ≥80 years, whereas severe dementia emerged is a relevant risk factor in this population. Severe COVID‐19, as expressed by elevated lactate dehydrogenase and low oxygen saturation at emergency department admission, is associated with a rapid progression to death in these patients. Geriatr Gerontol Int 2020; ••: ••–••.


title: 1 Libraries and risk

text: Abstract Risk is a constant feature of life. Librarians have often relied on others – including first responders, public health authorities and consultants – to help them prepare for and respond to risk. Many libraries lack effective disaster plans, which should cover the broad spectrum of risks: natural, technological, human-caused, proximity, security and enterprise. Human nature, exemplified by apathy, carelessness and inattention, can hinder planning efforts.


title: Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing

text: Abstract Background Viral respiratory tract infections and atopy are associated with attacks of wheezing during childhood. However, information about the relationship between viral infections and atopy among children whose attacks of wheezing lead to hospitalization is unclear. Objective To evaluate the prevalence of viral respiratory tract pathogens among infants and children hospitalized for wheezing and to analyze the results in relation to the patient's age, atopic characteristics, and season of admission. Methods This was a case-control study of children (age 2 months to 18 years) admitted for wheezing to the University of Virginia Medical Center over a period of 12 months. Children without wheezing were enrolled as controls. Nasal secretions were evaluated for viral pathogens by using cultures, PCR tests, and antigen detection. Total IgE and specific IgE antibody to common aeroallergens was measured in serum. Results Seventy percent of children hospitalized for wheezing before age 3 years (n=79) were admitted between December and March, whereas 46% of children age 3 to 18 years (n=54) were hospitalized between September and November. Among children younger than 3 years, viral pathogens were detected in 84% (66/79) of wheezing children and 55% (42/77) of controls (P < .001). Respiratory syncytial virus was the dominant pathogen during the winter months, but rhinovirus was more common during other months. Total serum IgE levels were generally low, and values from wheezing and control subjects overlapped considerably. Among children 3 years and older, 61% (33/54) of subjects admitted for wheezing tested positive for virus (predominantly rhinovirus), compared with 21% (12/56) of controls (P < .001). The total serum IgE values among wheezing children (geometric mean, 386 IU/mL; 95% CI, 259-573) were substantially elevated compared with those of controls (geometric mean, 38 IU/mL; 95% CI, 26-56; P < .001). A significantly higher percentage of wheezing children compared with controls was sensitized to at least 1 of the inhaled allergens tested: 84% (36/43) compared with 33% (15/45; P < .001). The atopic characteristics of wheezing children who tested positive or negative for virus were similar. Conclusions Viral infections were the dominant risk factor for wheezing among children hospitalized before 3 years of age. By comparison, a large majority of the wheezing children age 3 to 18 years had striking atopic characteristics that may be critical as a risk factor for hospitalization and an adverse response to viral infections, especially infections caused by rhinovirus.


title: Exploring the Impact of COVID-19 on Progress Towards Achieving Global Surgery Goals

text: INTRODUCTION: In the 5 months since it began, the COVID-19 pandemic has placed extraordinary demands on health systems around the world including surgery. Competing health objectives and resource redeployment threaten to retard the scale-up of surgical services in low- and middle-income countries where access to safe, affordable and timely care is low. The key aspiration of the Lancet Commission on global surgery was promotion of resilience in surgical systems. The current pandemic provides an opportunity to stress-test those systems and identify fault-lines that may not be easily apparent outside of times of crisis. METHODS: We endeavoured to explore vulnerable points in surgical systems learning from the experience of past outbreaks, using examples from the current pandemic, and make recommendations for future health emergencies. The 6-component framework for surgical systems planning was used to categorise the effects of COVID-19 on surgical systems, with a particular focus on low- and middle-income countries. Key vulnerabilities were identified and recommendations were made for the current pandemic and for the future. RESULTS: Multiple stress points were identified throughout all of the 6 components of surgical systems. The impact is expected to be highest in the workforce, service delivery and infrastructure domains. Innovative new technologies should be employed to allow consistent, high-quality surgical care to continue even in times of crisis. CONCLUSIONS: If robust progress towards global surgery goals for 2030 is to continue, the stress points identified should be reinforced. An ongoing process of reappraisal and fortification will keep surgical systems in low- and middle-income countries responsive to “old threats and new challenges”. Multiple opportunities exist to help realise the dream of surgical systems resilient to external shocks.


title: The Prevalence of Human Bocavirus, Human Coronavirus-NL63, Human Metapneumovirus, Human Polyomavirus KI and WU in Respiratory Tract Infections in Kuwait

text: OBJECTIVE: The aim of this study was to investigate the prevalence of human coronavirus (HCoV)-NL63, human metapneumovirus (hMPV), human bocavirus (Boca), human polyomavirus KI (KIV) and human polyomavirus WU (WUV) in respiratory tract infections (RTI) in Kuwait. MATERIALS AND METHODS: Respiratory samples from 735 hospitalized patients with RTI from September 2010 to April 2013 were evaluated for the presence of HCoV-NL63, hMPV, Boca, KIV and WUV using molecular assays, polymerase chain reaction (PCR) and reverse-transcription PCR. RESULTS: Of the 735 patients, 285 (38.8%) were diagnosed with viral RTI. The distribution of respiratory viruses was hMPV: 15 (5.3%), Boca: 14 (4.9%), WUV: 10 (3.5%) and KIV: 4 (1.4%). HCoV-NL63 was not detected in any of the samples. CONCLUSIONS: These newly discovered viruses were associated with the development of RTI in Kuwait. The rapid identification of these viral infections could aid in the control of nosocomial transmission, reduce the use of antibiotics and improve treatment and management strategies.


title: Commentary on “Health Spending Under Single-Payer Approaches”

text: One of the most controversial areas in discussions of single-payer approaches for the United States, such as “Medicare for All,” concerns its implications for costs. Confusion over differences between federal and total spending and effects of lower patient cost sharing gets in the way of “apples-to-apples” comparisons. Key areas with potential to lower costs are lower administrative costs and lower provider prices. But cost reduction would likely be smaller than some envision, especially in the price area because of the need for a long process to gradually allow providers to adjust to lower prices and Americans' unique attitudes toward regulation.


title: SARS in Pregnancy

text: While severe acute respiratory syndrome (SARS) is increasing in prevalence throughout the world, there had not been a documented case of SARS in pregnancy until early 2003, when a pregnant woman infected with SARS sought care at this New Jersey Hospital in March 2003. As this patient was the only known pregnant SARS patient in the U.S., there was a critical need to balance patient privacy, confidentiality, general care needs and support with a worldwide need for knowledge about the outcomes from SARS infections. Here's how the hospital staff worked with all of the agencies to develop protocols and coordinate this mother's and infant's care.


title: Early life rhinovirus wheezing, allergic sensitization, and asthma risk at adolescence

text: Background Early life rhinovirus (RV) wheezing illnesses and aeroallergen sensitization increase the risk of asthma at school age. Whether these remain risk factors for the persistence of asthma out to adolescence is not established. Objective We sought to define the relationships among specific viral illnesses and the type and timing of aeroallergen sensitization with the persistence of asthma into adolescence. Methods A total of 217 children were followed prospectively from birth to age 13 years. The etiology and timing of viral wheezing illnesses during the first 3 years of life were assessed along with patterns of allergen sensitization. The associations between viral wheezing illnesses, presence and pattern of aeroallergen sensitization, and asthma diagnosis at age 13 years were evaluated. Results When adjusted for all viral etiologies, wheezing with RV (odds ratio = 3.3; 95% CI, 1.5-7.1), but not respiratory syncytial virus (odds ratio = 1.0; 95% CI, 0.4-2.3), was associated with asthma at age 13 years. Age of aeroallergen sensitization also influenced asthma risk; 65% of children sensitized by age 1 year had asthma at age 13 years, compared with 40% of children not sensitized at age 1 year but sensitized by age 5 years, and 17% of children not sensitized at age 5 years. Early life aeroallergen sensitization and RV wheezing had additive effects on asthma risk at adolescence. Conclusions In a high-risk birth cohort, the persistence of asthma at age 13 years was most strongly associated with outpatient wheezing illnesses with RV and aeroallergen sensitization in early life.


Mayo Clinic Strategies for COVID-19 Engaging and Empowering the Front Lines During the COVID-19 Outpatient Practice Reactivation