title: The impact of type 2 diabetes and its management on the prognosis of patients with severe COVID‐19

text: BACKGROUND: Although T2DM patients with COVID‐19 develop a more severe condition compared to those without diabetes, the mechanisms for this are unknown. Moreover, the impact of treatment with anti‐hyperglycemic drugs and glucocorticoids is unclear. METHODS: From 1584 COVID‐19 patients, 364 severe/critical COVID‐19 patients with clinical outcome were enrolled for the final analysis and patients without pre‐existing T2DM but elevated glucose levels were excluded. Epidemiological data were obtained and clinical‐status evaluation carried out to assess the impact of T2DM and its management on clinical outcomes. RESULTS: Of 364 enrolled severe COVID‐19 inpatients, 114 (31.3%) cases had a history of T2DM. 27(23.7%) cases died in T2DM patients, who had more severe inflammation, coagulation activation, myocardia injury, hepatic injury, and kidney injury, compared with non‐DM patients. In severe COVID‐19 patients with T2DM, we demonstrate a higher risk of all‐cause fatality with glucocorticoid treatment (Adjusted HR, 3.61; 95%CI, 1.14‐11.46; P = 0.029), and severe hyperglycemia (FPG ≥11.1 mmol/L) (Adjusted HR, 11.86; 95%CI, 1.21‐116.44; P = 0.034). CONCLUSIONS: T2DM status aggravated the clinical condition of COVID‐19 patients and increased their critical illness risk. Poor fasting blood glucose (≥ 11.1 mmol/L) and glucocorticoid treatment are associated with poor prognosis for T2DM patients with severe COVID‐19. This article is protected by copyright. All rights reserved.


title: Patient outcomes after humeral fracture surgery during the COVID-19 outbreak in Spain

text: Abstract Background The global spread of the 2019 novel coronavirus (COVID-19) has profoundly affected the way we conduct our healthcare practices. The goal of this paper is to report the outcomes of 11 patients who underwent humeral fracture surgery in the first few weeks of the COVID-19 outbreak in Spain. Methods This was a retrospective case series of 11 patients who underwent humeral fracture surgery during the first weeks of the COVID-19 outbreak in Spain, between 10 March and 25 April 2020. The clinical outcomes of these operative patients were monitored up to 12 May 2020, the final date of follow-up, a minimum of 15 days after all patients were discharged from the hospital. COVID-19 infection, mortality, demographic, clinical, and laboratory data were analyzed. Results Thirty-six humeral fractures were recorded between 10 March and 25 April 2020. During this period, humeral fracture fixation was the third most common surgery for fracture in our institution after hip fracture and ankle fracture surgery. Eleven patients underwent surgery (30.5%), of which seven were women (63.3%). The mean age was 64.8 years (SD 13.5). Nine operated cases had a proximal humerus fracture and 2 had a humeral shaft fracture. One of the 11 patients was positive for SARS-CoV-2 on the basis of quantitative reverse transcription polymerase chain reaction (RT-PCR) of throat swab samples. The overall median surgical time was 101.2 minutes (SD 28.4). The overall median hospital length stays for the patient discharged was 2.2 days (range 1-4). No COVID-19 nosocomial intrahospital infection occurred, no patient reported COVID-19 infection during the 15 days after hospital discharge. No intrahospital mortality was recorded. Furthermore, no COVID-19 infection was reported in the shoulder surgeons that performed the surgeries. Conclusions Although humeral fractures were not the most frequent fracture during this outbreak, some required surgery. With good preoperative management that included RT-PCR for COVID-19 and chest radiographs, protective measurements for the surgical team, and rapid discharge of the patients, we were able to operate on 11 humeral fractures with no COVID-19 nosocomial intrahospital infection in the patients or in the shoulder surgeons that performed the surgeries.


title: Survivors of COVID-19 are at high risk of posttraumatic stress disorder

text: Posttraumatic stress disorder (PTSD) is a common mental disorder caused by major psychological trauma. It could result in serious distress and disability. Previous epidemic studies report high prevalence rates among people exposed to the trauma resulted from an infectious disease epidemic. While the control of the epidemic and care of patients with COVID-19 are still the dominant task of the whole world, this commentary calls for attention to early intervention and prevention of PTSD among huge numbers of COVID-19 survivors, their family members, health care professionals and other first-line helpers.


title: Deconvoluting Lipid Nanoparticle Structure for Messenger RNA Delivery

text: [Image: see text] Lipid nanoparticle (LNP) packaged mRNA vaccines have been deployed against infectious diseases such as COVID-19, yet their structural features remain unclear. Cholesterol, a major constituent within LNPs, contributes to their morphology that influences gene delivery. Herein, we examine the structure of LNPs containing cholesterol derivatives using electron microscopy, differential scanning calorimetry, and membrane fluidity assays. LNPs formulated with C24 alkyl derivatives of cholesterol show a polymorphic shape and various degrees of multilamellarity and lipid partitioning, likely due to phase separation. The addition of methyl and ethyl groups to the C24 alkyl tail of the cholesterol backbone induces multilamellarity (>50% increase compared to cholesterol), while the addition of a double bond induces lipid partitioning (>90% increase compared to cholesterol). LNPs with multilamellar and faceted structures, as well as a lamellar lipid phase, showed higher gene transfection. Unraveling the structure of mRNA-LNPs can enable their rational design toward enhanced gene delivery.


docid: dcuwmfim

title: “Xenophobia in America in the Age of Coronavirus and Beyond”


Viscoelastic testing in COVID‐19: a possible screening tool for severe disease?


title: Multifaceted Regulation of Translational Readthrough by RNA Replication Elements in a Tombusvirus

text: Translational readthrough of stop codons by ribosomes is a recoding event used by a variety of viruses, including plus-strand RNA tombusviruses. Translation of the viral RNA-dependent RNA polymerase (RdRp) in tombusviruses is mediated using this strategy and we have investigated this process using a variety of in vitro and in vivo approaches. Our results indicate that readthrough generating the RdRp requires a novel long-range RNA-RNA interaction, spanning a distance of ∼3.5 kb, which occurs between a large RNA stem-loop located 3'-proximal to the stop codon and an RNA replication structure termed RIV at the 3'-end of the viral genome. Interestingly, this long-distance RNA-RNA interaction is modulated by mutually-exclusive RNA structures in RIV that represent a type of RNA switch. Moreover, a different long-range RNA-RNA interaction that was previously shown to be necessary for viral RNA replicase assembly was also required for efficient readthrough production of the RdRp. Accordingly, multiple replication-associated RNA elements are involved in modulating the readthrough event in tombusviruses and we propose an integrated mechanistic model to describe how this regulatory network could be advantageous by (i) providing a quality control system for culling truncated viral genomes at an early stage in the replication process, (ii) mediating cis-preferential replication of viral genomes, and (iii) coordinating translational readthrough of the RdRp with viral genome replication. Based on comparative sequence analysis and experimental data, basic elements of this regulatory model extend to other members of Tombusviridae, as well as to viruses outside of this family.


title: Incorporating Video Visits into Ophthalmology Practice: A Retrospective Analysis and Patient Survey to Assess Initial Experiences and Patient Acceptability at an Academic Eye Center

text: INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has led to rapid adoption of teleophthalmology to deliver eyecare remotely. The purpose of our study was to assess the implementation and patient acceptability of video consultation for outpatient ophthalmic care at our institution. METHODS: We conducted a retrospective, cross-sectional analysis and patient survey of adult patients who completed a virtual video visit at our institution from 18 March 18 through to 27 April 2020. All video visit encounters were assessed for patient characteristics, diagnoses, management, and follow-up outcomes. Patients were surveyed for their feedback on acceptability and utility of their virtual video consultation. RESULTS: A total of 219 patients (mean age 55 years; range 21–89 years) completed 231 video visit encounters at our department over a 6-week period, of whom 118 were women (54%). About half of these encounters were acute visits (102 visits, 47%). The most common diagnosis of these visits was postoperative state (20 visits, 9% of the total), followed by conjunctivitis (16 visits, 7%), and keratitis (14 visits, 6%). The most common management decisions were medication prescription (102 visits, 46%) or reassurance (86 visits, 39%), while 17 video visit patients (8%) were escalated to an urgent, in-person evaluation. Ninety-two patients completed a follow-up survey (42% response rate), of whom 45 (49%) indicated that they might have delayed seeking care during this pandemic in the absence of a virtual video option. Seventy-two (78%) reported that they would consider participating in a video visit as an alternative to an office-based encounter in the future, and the overall video visit experience was rated highly, with a weighted mean Likert scale rating of 4.3 out of 5 (Cronbach’s α = 0.88). CONCLUSION: Virtual video visits may be used to manage a range of ophthalmic complaints. Patients participating in this survey found such video visits acceptable and timesaving, and the majority would consider using video consultations for future eyecare encounters.


title: Aetiology of febrile pharyngitis in children: Potential of myxovirus resistance protein A (MxA) as a biomarker of viral infection

text: Summary Objectives Besides group A streptococcus (GAS), microbial causes of pharyngitis in children are not well known. We aimed to document the viral and bacterial aetiology of pharyngitis and to assess the pathogenic role of viruses by determining the myxovirus resistance protein A (MxA) in the blood as a marker of interferon response. Methods In this prospective observational study, throat swabs and blood samples were collected from children (age 1–16 years) presenting to the emergency department with febrile pharyngitis. Microbial cause was sought by bacterial culture, polymerase chain reaction, and serology. Blood MxA level was determined. Results A potential pathogen was detected in 88% of 83 patients: GAS alone in 10%, GAS and viruses in 13%, group C or G streptococci alone in 2% and together with viruses in 3%, and viruses alone in 59% of cases. Enteroviruses, rhinoviruses, and adenoviruses were the most frequently detected viruses. Blood MxA levels were higher in children with viral (880 [245–1250] μg/L; median [IQR]) or concomitant GAS-viral (340 [150–710] μg/L) than in those with sole GAS (105 [80–160] μg/L) infections. Conclusions Detection of respiratory viruses simultaneously with elevated blood MxA levels supports the causative role of viruses in the majority of children with pharyngitis.


title: Detection of Bovine Coronavirus in Healthy and Diarrheic Dairy Calves

text: BACKGROUND: BCoV is identified in both healthy and diarrheic calves, complicating its assessment as a primary pathogen. OBJECTIVES: To investigate the detection rates of bovine coronavirus (BCoV) in feces of healthy and diarrheic calves and to describe the usefulness of a pancoronavirus reverse transcriptase (RT) PCR (PanCoV‐RT‐PCR) assay to identify BCoV in samples of diarrheic calves. ANIMALS: Two hundred and eighty‐six calves <21 days. Calves with liquid or semiliquid feces, temperature >39.5°C, and inappetence were considered as cases, and those that had pasty or firm feces and normal physical examination were designated as controls. METHODS: Prospective case–control study. A specific BCoV‐RT‐PCR assay was used to detect BCoV in fecal samples. Association between BCoV and health status was evaluated by exact and random effect logistic regression. Fecal (n = 28) and nasal (n = 8) samples from diarrheic calves were tested for the presence of BCoV by both the PanCoV‐RT‐PCR and a specific BCoV‐RT‐PCR assays. A Kappa coefficient test was used to assess the level of agreement of both assays. RESULTS: BCoV was detected in 55% (157/286) of calves; 46% (66/143), and 64% (91/143) of healthy and diarrheic calves, respectively. Diarrheic calves had higher odds of BCoV presence than healthy calves (OR: 2.16, 95% CI: 1.26 to 3.83, P = 0.004). A good agreement between PanCoV‐RT‐PCR and BCoV‐RT‐PCR to detect BCoV was identified (κ = 0.68, 95% CI: 0.392 to 0.967; P < 0.001). CONCLUSIONS AND CLINICAL IMPORTANCE: BCoV was more likely to be detected in diarrheic than healthy calves. The PanCoV‐RT‐PCR assay can be a useful tool to detect CoV samples from diarrheic calves.


title: Transmission of SARS in three Chinese hospitals

text: Objective To quantify the transmissibility of severe acute respiratory syndrome (SARS) in hospitals in mainland China and to assess the effectiveness of control measures. Methods We report key epidemiological details of three major hospital outbreaks of SARS in mainland China, and estimate the evolution of the effective reproduction number in each of the three hospitals during the course of the outbreaks. Results The three successive hospital outbreaks infected 41, 99 and 91 people of whom 37%, 60% and 70% were hospital staff. These cases resulted in 33 deaths, five of which occurred in hospital staff. In a multivariate logistic regression, age and whether or not the case was a healthcare worker (HCW) were found to be significant predictors of mortality. The estimated effective reproduction numbers (95% CI) for the three epidemics peaked at 8 (5, 11), 9 (4, 14) and 12 (7, 17). In all three hospitals the epidemics were rapidly controlled, bringing the reproduction number below one within 25, 10 and 5 days respectively. Conclusions This work shows that in three major hospital epidemics in Beijing and Tianjin substantially higher rates of transmission were initially observed than those seen in the community. In all three cases the hospital epidemics were rapidly brought under control, with the time to successful control becoming shorter in each successive outbreak.


title: Aminopeptidase N in arterial hypertension

text: Aminopeptidase N (APN) or CD13 is a conserved type II integral membrane zinc-dependent metalloprotease in the M1 family of ectoenzymes. APN is abundant in the kidneys and central nervous system. Identified substrates include Angiotensin III (Ang III); neuropeptides, including enkephalins and endorphins; and homones, including kallidan and somatostatin. It is developmentally expressed, a myelomonocytic marker for leukemias, and a receptor for coronovirus. There is evolving support for APN in the regulation of arterial blood pressure and the pathogenesis of hypertension. In rodent strains, intracerebraventricular (i.c.v.) infusions of APN reduces, while inhibitors of APN activity have a pressor effect on blood pressure. Dysregulation of central APN has been linked to the pathogenesis of hypertension in the spontaneously hypertensive rat. There is evidence that renal tubule APN inhibits Na flux and plays a mechanistic role in salt-adaptation. A functional polymorphism of the ANP gene has been identified in the Dahl salt-sensitive rat. Signaling by APN impacting on blood pressure is likely mediated by regulation of the metabolism of Ang III to Ang IV. Whether APN regulates arterial blood pressure in humans or is a therapeutic target for hypertension are subjects for future exploration.


title: Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses

text: Human coronaviruses (HCoVs) were first described in the 1960s for patients with the common cold. Since then, more HCoVs have been discovered, including those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), two pathogens that, upon infection, can cause fatal respiratory disease in humans. It was recently discovered that dromedary camels in Saudi Arabia harbor three different HCoV species, including a dominant MERS HCoV lineage that was responsible for the outbreaks in the Middle East and South Korea during 2015. In this review we aim to compare and contrast the different HCoVs with regard to epidemiology and pathogenesis, in addition to the virus evolution and recombination events which have, on occasion, resulted in outbreaks amongst humans.


title: HIV-1 Frameshift RNA-Targeted Triazoles Inhibit Propagation of Replication-Competent and Multi-Drug-Resistant HIV in Human Cells

text: [Image: see text] The HIV-1 frameshift-stimulating (FSS) RNA, a regulatory RNA of critical importance in the virus’ life cycle, has been posited as a novel target for anti-HIV drug development. We report the synthesis and evaluation of triazole-containing compounds able to bind the FSS with high affinity and selectivity. Readily accessible synthetically, these compounds are less toxic than previously reported olefin congeners. We show for the first time that FSS-targeting compounds have antiviral activity against replication-competent HIV in human cells, including a highly cytopathic, multidrug-resistant strain. These results support the viability of the HIV-1 FSS RNA as a therapeutic target and more generally highlight opportunities for synthetic molecule-mediated interference with protein recoding in a wide range of organisms.


title: Décès brutal et infection à virus Influenza A chez un enfant de deux ans : étude d’un cas autopsique

text: Résumé La grippe de l’enfant est fréquente mais passe souvent inaperçue. Les formes gravissimes ou létales sont en revanche exceptionnelles. Observation. – Nous rapportons une observation de décès brutal d’un enfant de 23 mois chez lequel le virus Influenza A a été isolé postmortem par polymerase chain reaction (PCR) dans le poumon et dont les lésions anatomopathologiques étaient celles décrites dans la grippe maligne. Conclusion. – Devant un tableau de décès non expliqué voire une mort subite du nourrisson ou du jeune enfant, les causes infectieuses en particulier virales doivent être cherchées soigneusement avec recherche virale par PCR recommandée, les autres techniques pouvant rester négatives. Abstract Influenza A virus infections are common in childhood and infancy and are often underdiagnosed while serious or letal forms are rare. Case-report. – We describe a case of sudden death in a two-year-old boy. Pathologic findings at autopsy were consistent with Myxovirus influenzae A virus infection and the virus was isolated by post mortem PCR. Conclusion. – In the case of sudden death in infants, especially if pathologic findings are compatible with a viral infection, PCR may allow identification of the causative virus.


title: Evolutionary characterization of the emerging porcine epidemic diarrhea virus worldwide and 2014 epidemic in Taiwan

text: Abstract Since 2010, a new variant of PEDV belonging to Genogroup 2 has been transmitting in China and further spreading to the Unites States and other Asian countries including Taiwan. In order to characterize in detail the temporal and geographic relationships among PEDV strains, the present study systematically evaluated the evolutionary patterns and phylogenetic resolution in each gene of the whole PEDV genome in order to determine which regions provided the maximal interpretative power. The result was further applied to identify the origin of PEDV that caused the 2014 epidemic in Taiwan. Thirty-four full genome sequences were downloaded from GenBank and divided into three non-mutually exclusive groups, namely, worldwide, Genogroup 2 and China, to cover different ranges of secular and spatial trends. Each dataset was then divided into different alignments by different genes for likelihood mapping and phylogenetic analysis. Our study suggested that both nsp3 and S genes contained the highest phylogenetic signal with substitution rate and phylogenetic topology similar to those obtained from the complete genome. Furthermore, the proportion of nodes with high posterior support (posterior probability >0.8) was similar between nsp3 and S genes. The nsp3 gene sequences from three clinical samples of swine with PEDV infections were aligned with other strains available from GenBank and the results suggested that the virus responsible for the 2014 PEDV outbreak in Taiwan clustered together with Clade I from the US within Genogroup 2. In conclusion, the current study identified the nsp3 gene as an alternative marker for a rapid and unequivocal classification of the circulating PEDV strains which provides complementary information to the S gene in identifying the emergence of epidemic strain resulting from recombination.


title: Psychological responses of pregnant women to an infectious outbreak: A case-control study of the 2003 SARS outbreak in Hong Kong

text: Abstract Objective The aim of the present study was to examine the behavioral and psychological responses of pregnant women during the 2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong. Methods Ethnographic interviews were first conducted to identify the common psychological and behavioral responses to the outbreak. This was followed by a case-control study of 235 consecutive pregnant women recruited during the SARS epidemic, and a historical cohort of 939 pregnant women recruited a year before the outbreak. Both cohorts completed standardized rating scales on depression, anxiety, and social support. Results Women in the SARS cohort adopted behavioral strategies to mitigate their risk of contracting infection. However, pregnant women tended to overestimate the risk of contracting SARS and nearly a third of the women were homebound. The anxiety level of the SARS cohort was slightly higher than that of the pre-SARS control. No statistical difference was found between the depression levels of the two cohorts. Conclusion The improved social support experienced by pregnant women during SARS might have buffered the stress associated with an outbreak. However, clinicians should monitor for overestimation of infectious risk among pregnant women.


title: COVID‐19 patients with psoriasis and psoriatic arthritis on biologic immunosuppressant therapy versus apremilast in North Spain

text: Immunosuppressive and immunomodulatory treatments are critical for the management of inflammatory and autoimmune conditions such as psoriasis or psoriatic arthritis. Like in those illnesses, the lung injury and acute respiratory distress shown in COVID‐19 patients are the result of a disruption in the balance of pro‐ and anti‐inflammatory cytokines. This hyperinflammatory response to SARS‐CoV‐2, associated with the severity of the coronavirus disease, is called the cytokine storm. There is a growing concern regarding how patients on immunosuppressant biologic therapies might be at higher risk of being infected and whether they need to discontinue their treatment preemptively. Clinical data on COVID‐19 infected patients with psoriasis or psoriatic arthritis are still scarce. Here, we presented seven cases of this type of patients. The patient infected with COVID‐19 on apremilast and the one on apremilast with infected spouse showed the best safety profile and mildest symptoms. One of the secukinumab patients also presented a relatively good outcome. Infliximab patients and the one with serious comorbidities showed the worst outcome. Even though more clinical data are yet needed to draw strong conclusions, apremilast could be a safer alternative for dermatology and rheumatology patients in case of clinically important active infection. This article is protected by copyright. All rights reserved.


Introduction to Clinical Answers: Croup


title: Global Distribution of Infectious Diseases Requiring Intensive Care

text: This article describes infectious diseases that are of special importance to intensivists. The emphasis on epidemiology notwithstanding, it also addresses clinical, diagnostic, and treatment issues related to each infection described. The discussion avoids terrorism-related aspects of these infections, because they were very well covered in the October 2005 issue of the Critical Care Clinics.


title: Nasal-Swab Testing Misses Patients with Low SARS-CoV-2 Viral Loads

text: The urgent need for large-scale diagnostic testing for SARS-CoV-2 has prompted pursuit of sample-collection methods of sufficient sensitivity to replace sampling of the nasopharynx (NP). Among these alternatives is collection of nasal-swab samples, which can be performed by the patient, avoiding the need for healthcare personnel and personal protective equipment. Previous studies have reached opposing conclusions regarding whether nasal sampling is concordant or discordant with NP. To resolve this disagreement, we compared nasal and NP specimens collected by healthcare workers in a cohort consisting of individuals clinically suspected of COVID-19 and outpatients known to be SARS-CoV-2 RT-PCR positive undergoing follow-up. We investigated three different transport conditions, including traditional viral transport media (VTM) and dry swabs, for each of two different nasal-swab collection protocols on a total of 308 study participants, and compared categorical results and Ct values to those from standard NP swabs collected at the same time from the same patients. All testing was performed by RT-PCR on the Abbott SARS-CoV-2 RealTime EUA (limit of detection [LoD], 100 copies viral genomic RNA/mL transport medium). We found high concordance (Cohen’s kappa >0.8) only for patients with viral loads above 1,000 copies/mL. Those with viral loads below 1,000 copies/mL, the majority in our cohort, exhibited low concordance (Cohen’s kappa = 0.49); most of these would have been missed by nasal testing alone. Previous reports of high concordance may have resulted from use of assays with higher LoD (≥1,000 copies/mL). These findings counsel caution in use of nasal testing in healthcare settings and contact-tracing efforts, as opposed to screening of asymptomatic, low-prevalence, low-risk populations. Nasal testing is an adjunct, not a replacement, for NP.


title: Experience with a Multinational, Secondary School Education Module with a Focus on Prevention of Virus Infections

text: Worldwide, virus infections are responsible for many diseases in terms of morbidity and mortality. Vaccinations and therapies are only available for relatively few virus infections and not always where they are needed. However, knowledge of transmission routes can prevent virus infection. In the context of this study, we measured the effects of a secondary school education module, named Viruskenner, on knowledge, attitude, and risk behavior as these relate to virus infections. A nonrandomized intervention study was conducted between April and August 2015 to assess the effect of this 2-month education module on knowledge, attitude, and behavior of 684 secondary school students in the Netherlands, Suriname, and Indonesia. For the Netherlands, a control group of a further 184 students was added. Factor analysis was performed on questions pertaining to attitude and behavior. Comparative analyses between pre- and posttest per country were done using multiple linear regression, independent sample T-tests, and one-way analysis of variance. These showed a significant increase in knowledge about virus infections and the prevention of infectious diseases among the Dutch and Surinamese groups, whereas a trend of increased knowledge was evident among the Indonesian participants. The Dutch control group showed an overall decrease in knowledge. Regression analyses showed that there was a significant interaction effect between participation and time on knowledge, attitude, and awareness and behavior and risk infection. Attitudes improved significantly in the intervention group. Pearson correlation coefficients between knowledge, attitude, and behavior were found to be positive.


title: Evaluation of serum protein-based arrival formula and serum protein supplement (Gammulin) on growth, morbidity, and mortality of stressed (transport and cold) male dairy calves

text: Abstract Previous studies with calves and other species have provided evidence that blood serum-derived proteins and fructooligosaccharides (FOS) may benefit intestinal health. We assessed the effects of supplementing products containing serum proteins as a component of arrival fluid support or serum proteins plus FOS (in addition to additional solids, minerals, and vitamins) in an early life dietary supplement on performance, morbidity, and mortality of stressed (transport, cold) male calves. Male Holstein calves (n=93) <1 wk old were stratified by arrival body weight (BW) and plasma protein concentration, and then randomly assigned to 1 of 4 treatment groups in a 2×2 factorial arrangement of one-time administration of fluid support [either control electrolyte solution (E) or the serum protein-containing arrival formula (AF)] and 14d of either no supplementation (NG) or supplementation with Gammulin (G; APC Inc., Ankeny, IA), which contains serum proteins and FOS in addition to other solids, minerals, and vitamins. Upon arrival at the research facility, calves were orally administered either AF or E. At the next feeding, half of the calves from each fluid support treatment received either milk replacer (20% crude protein, 20% fat) or the same milk replacer supplemented with G (50g/d during the first 14d). Starter and water were freely available. Feed offered and refused was recorded daily. Calf health was assessed by daily assignment of fecal and respiratory scores. Stature measures and BW were determined weekly. Blood samples were obtained at d 0 (before treatments), 2, 7, 14, and 28. Calves were weaned at d 42 and remained in the experiment until d 56. After 2 wk of treatments, calves previously fed AF had greater body length (66.6 vs. 66.0cm), intakes of dry matter (38.7 vs. 23.5g/d) and crude protein (9.2 vs. 5.6g/d) from starter, and cortisol concentration in blood (17.0 vs. 13.9 ng/mL) than calves fed E. Supplementation with G resulted in greater BW gain during the first 2 wk, increased intakes of dry matter and CP, and decreased respiratory scores. For the 8-wk experiment, G supplementation resulted in lower mean fecal score (1.6 vs. 1.8) and fewer antibiotic treatments per calf (1.5 vs. 2.5) than NG. Survival was greater in G than in NG calves (98 vs. 84%). Despite the marked reduction in morbidity and mortality, blood indicators of acute-phase response, urea N, and total protein were not affected by AF or G in transported cold-stressed male calves.


title: Neutralization of budded Autographa californica NPV by a monoclonal antibody: Identification of the target antigen

text: Abstract A neutralizing monoclonal antibody of the budded phenotype of Autographa californica nuclear polyhedrons virus did not react with the occluded form of the virus as determined by neutralization, ELISA, and indirect immunoperoxidase staining. The antibody did react with the surface of infected cells in the prepolyhedra stage of cytopathic effect, the period of active virus budding. Immunoelectron microscopy indicated the antigen(s) reactive with the neutralizing antibody was present all around the viral envelope, but was more highly concentrated at the end with peplomers. Four proteins were immunoprecipitated from solubilized, radiolabeled budded virus preparations with the monoclonal antibody. The major protein had a molecular weight of approximately 64,000, while the other three were approximately 127,000, 59,000, and 49,000. All four proteins could be labeled with N-acetyl-d-[1-3H]glucosamine. This glycosylation reaction could be inhibited by tunicamycin.


title: Establishment of serological test to detect antibody against ferret coronavirus

text: Since there is no available serological methods to detect antibodies to ferret coronavirus (FRCoV), an enzyme-linked immunosorbent assay (ELISA) using recombinant partial nucleocapsid (N) proteins of the ferret coronavirus (FRCoV) Yamaguchi-1 strain was developed to establish a serological method for detection of FRCoV infection. Many serum samples collected from ferrets recognized both a.a. 1–179 and a.a. 180–374 of the N protein, but two serum samples did not a.a. 180–374 of the N protein. This different reactivity was also confirmed by immunoblot analysis using the serum from the ferret.Therefore, the a.a. 1–179 of the N protein was used as an ELISA antigen. Serological test was carried out using sera or plasma of ferrets in Japan. Surprisingly, 89% ferrets in Japan had been infected with FRCoV. These results indicated that our established ELISA using a.a. 1–179 of the N protein is useful for detection of antibody to FRCoV for diagnosis and seroepidemiology of FRCoV infection.


title: Dysphagia Care Across the Continuum: A Multidisciplinary Dysphagia Research Society Taskforce Report of Service-Delivery During the COVID-19 Global Pandemic

text: At the time of writing this paper, there are over 11 million reported cases of COVID-19 worldwide. Health professionals involved in dysphagia care are impacted by the COVID-19 pandemic in their day-to-day practices. Otolaryngologists, gastroenterologists, rehabilitation specialists, and speech-language pathologists are subject to virus exposure due to their proximity to the aerodigestive tract and reliance on aerosol-generating procedures in swallow assessments and interventions. Across the globe, professional societies and specialty associations are issuing recommendations about which procedures to use, when to use them, and how to reduce the risk of COVID-19 transmission during their use. Balancing safety for self, patients, and the public while maintaining adequate evidence-based dysphagia practices has become a significant challenge. This paper provides current evidence on COVID-19 transmission during commonly used dysphagia practices and provides recommendations for protection while conducting these procedures. The paper summarizes current understanding of dysphagia in patients with COVID-19 and draws on evidence for dysphagia interventions that can be provided without in-person consults and close proximity procedures including dysphagia screening and telehealth.


title: Therapeutic Drugs Targeting 2019-nCoV Main Protease by High-Throughput Screening

text: 2019 Novel Coronavirus (2019-nCoV) is a virus identified as the cause of the outbreak of pneumonia first detected in Wuhan, China. Investigations on the transmissibility, severity, and other features associated with this virus are ongoing. Currently, there is no vaccine or therapeutic antibody to prevent the infection, and more time is required to develop an effective immune strategy against the pathogen. In contrast, specific inhibitors targeting the key protease involved in replication and proliferation of the virus are the most effective means to alleviate the epidemic. The main protease of SARS-CoV is essential for the life cycle of the virus, which showed 96.1% of similarity with the main proteaseof 2019-nCoV, is considered to be an attractive target for drug development. In this study, we have identified 4 small molecular drugs with high binding capacity with SARS-CoV main protease by high-throughput screening based on the 8,000 clinical drug libraries, all these drugs have been widely used in clinical applications with guaranteed safety, which may serve as promising candidates to treat the infection of 2019-nCoV.


title: Superspreading SARS Events, Beijing, 2003

text: Superspreading events were pivotal in the global spread of severe acute respiratory syndrome (SARS). We investigated superspreading in one transmission chain early in Beijing’s epidemic. Superspreading was defined as transmission of SARS to at least eight contacts. An index patient with onset of SARS 2 months after hospital admission was the source of four generations of transmission to 76 case-patients, including 12 healthcare workers and several hospital visitors. Four (5%) case circumstances met the superspreading definition. Superspreading appeared to be associated with older age (mean 56 vs. 44 years), case fatality (75% vs. 16%, p = 0.02, Fisher exact test), number of close contacts (36 vs. 0.37) and attack rate among close contacts (43% vs. 18.5%, p < 0.025). Delayed recognition of SARS in a hospitalized patient permitted transmission to patients, visitors, and healthcare workers. Older age and number of contacts merit investigation in future studies of superspreading.


title: Laboratory diagnosis of human seasonal and pandemic influenza virus infection

text: Laboratory diagnosis is important to distinguish influenza from other respiratory virus infections. It will be especially important in detecting the first cases of pandemic influenza. Good quality respiratory tract sampling is needed to maximise diagnostic yield in influenza infection. In the appropriate clinical setting, pandemic strain‐specific nucleic acid testing is the initial test of choice for suspected pandemic influenza. It is more sensitive than virus isolation, and more sensitive and specific than serology, immunofluorescence and other antigen detection methods. Virus isolation is needed to monitor new influenza strains and for vaccine development. Analysis of influenza isolates is undertaken by the World Health Organization Global Influenza Surveillance Network. Monitoring for antiviral resistance will be needed with widespread use of neuraminidase inhibitors for treatment and prophylaxis during a pandemic.


Telehealth and Telemedicine in the COVID-19 era: A World of Opportunities for the Neurosurgeons.


title: Effect of different vaccination strategies on IBV QX population dynamics and clinical outbreaks

text: The extreme variability and rapid evolution of Infectious bronchitis virus (IBV) has always represented the key challenge for its control because of the limited cross-protection among different strains. Several experimental trials have proven a broadening of the protection spectrum when animals are vaccinated with multiple genotypes. Nevertheless, the conditions of vaccine administration in field are so different that the generalization of experimental results is, at least, questionable. In the present study a large scale epidemiological-phylodynamic approach was used to reconstruct the demographic history of the major field genotype (i.e. the QX one) circulating in Italy and Spain. These two countries were selected because, even if they share a comparable epidemiological scenario, the implemented vaccination protocols did not vary in Spain while changed dramatically in Italy over the time period considered. One hundred and ninety-five Italian and 98 Spanish non-recombinant sequences of the hyper-variable region of the S1 gene obtained between 2012 and 2016 were analyzed using a serial coalescent-based approach to reconstruct viral population history over time. While the IBV QX population dynamics remained constant in Spain, a much more complex pattern was evidenced in Italy; both in terms of viral population size and clinical outbreak frequency. Remarkably, a strong association with changes in vaccination strategies was recognized. This allowed demonstrating, by accomplishing all Hill’s criteria for causation, the cause-effect relationship between the vaccine administration/withdrawal and the variation in viral population dynamics and, above all, IBV related outbreaks. Thus, a robust confirmation about the efficacy of IBV vaccination in field conditions was provided. Additionally, the history herein reported testifies the primary importance of rigorously planning not only the intervention strategies but also their monitoring and evaluation.


title: Molecular characterization and pathogenicity of a genogroup GVI feline norovirus

text: Abstract Norovirus (NoV) has been classified into 6 genogroups, GI-GVI. In the present study, we identified novel feline NoV (FNoV) M49-1 strain. The C-terminal of RNA-dependent RNA polymerase of the FNoV M49-1 strain was highly homologous with GIV FNoV and GIV lion norovirus, whereas VP1 was highly homologous with GVI canine NoV (CNoV). Based on the results of the Simplot analysis, the FNoV M49-1 strain may have been produced by recombination between GIV.2 FNoV and GVI.1 CNoV. In addition, specific pathogen-free cats inoculated with FNoV gene-positive-fecal samples developed diarrhea symptoms, and the viral gene was detected in their feces and blood.


title: Innovative highlights of clinical drug trial design

text: Clinical trials serve as the gold standard to evaluate the efficacy and safety of tested drugs prior to marketing authorization. Nevertheless, there have been a few challenging issues well noted in traditional clinical trials such as tedious processing duration and escalating high costs among others. To improve the efficiency of clinical studies, a spectrum of expedited clinical trial modes has been designed, and selectively implemented in contemporary drug developing landscape. Herein this article presents an update on the innovated human trial designs that are corroborated through coming up with approval of notable therapeutic compounds for clinical utilization including delivery of several blockbuster products. It is intended to inspire clinical investigators and pharmaceutical development not only timely communicating with the regulatory agencies, but also insightful translating from cutting-edge scientific discoveries.


title: School absenteeism among school‐aged children with medically attended acute viral respiratory illness during three influenza seasons, 2012‐2013 through 2014‐2015

text: BACKGROUND: Acute respiratory illnesses (ARIs) are common in school‐aged children, but few studies have assessed school absenteeism due to specific respiratory viruses. OBJECTIVE: To evaluate school absenteeism among children with medically attended ARI due to common viruses. METHODS: We analyzed follow‐up surveys from children seeking care for acute respiratory illness who were enrolled in the influenza vaccine effectiveness study at Marshfield Clinic during the 2012‐2013 through 2014‐2015 influenza seasons. Archived influenza‐negative respiratory swabs were retested using multiplex RT‐PCR to detect 16 respiratory virus targets. Negative binomial and logistic regression models were used to examine the association between school absence and type of respiratory viruses; endpoints included mean days absent from school and prolonged (>2 days) absence. We examined the association between influenza vaccination and school absence among children with RT‐PCR‐confirmed influenza. RESULTS: Among 1027 children, 2295 days of school were missed due to medically attended ARIs; influenza accounted for 39% of illness episodes and 47% of days missed. Mean days absent were highest for influenza (0.96‐1.19) and lowest for coronavirus (0.62). Children with B/Yamagata infection were more likely to report prolonged absence than children with A/H1N1 or A/H3N2 infection [OR (95% CI): 2.1 (1.0, 4.5) and 1.7 (1.0, 2.9), respectively]. Among children with influenza, vaccination status was not associated with prolonged absence. CONCLUSIONS: School absenteeism due to medically attended ARIs varies by viral infection. Influenza B infections accounted for the greatest burden of absenteeism.


title: RESPUESTA INFLAMATORIA EN RELACIÓN A COVID-19 Y OTROS FENOTIPOS PROTROMBÓTICOS

text: Resumen El sistema hemostático actúa en concierto con la inflamación, de forma que tras la respuesta inflamatoria diversos mediadores activan el sistema hemostático a través de disfunción endotelial, activación plaquetar y de coagulación, promoviendo la trombosis, lo que se ha denominado tromboinflamación. En este proceso adquiere especial relevancia el inflamasoma, cuya estimulación promueve respuestas inmunes innata y adaptativa. La activación del inflamasoma juega un papel fisopatológico importante en diversas patologías que cursan con fenómenos inflamatorios y trombóticos. El papel de la tromboinflamación se ha puesto de relevancia en la pandemia por COVID-19, en la que se ha descrito una tormenta de citocinas como uno de los mecanismos responsables. Abstract The haemostatic system acts in concert with inflammation, so that after inflammatory response various mediators activate the haemostatic system through endothelial dysfunction, platelet activation and coagulation promoting thrombosis, which is termed thromboinflammation. In this process, the inflammasome acquires special relevance; its stimulation promotes innate and adaptive immune responses. Inflammasome activation plays an important physiopathological role in several disorders with inflammatory and thrombotic phenomena. The role of thromboinflammation has become relevant in the COVID-19 pandemic, in which a cytokine storm has been described as one of the mechanisms responsible.


title: Using Pan RNA-Seq Analysis to Reveal the Ubiquitous Existence of 5′ and 3′ End Small RNAs

text: In this study, we used pan RNA-seq analysis to reveal the ubiquitous existence of both 5′ and 3′ end small RNAs (5′ and 3′ sRNAs). 5′ and 3′ sRNAs alone can be used to annotate nuclear non-coding and mitochondrial genes at 1-bp resolution and identify new steady RNAs, which are usually transcribed from functional genes. Then, we provided a simple and cost effective way for the annotation of nuclear non-coding and mitochondrial genes and the identification of new steady RNAs, particularly long non-coding RNAs (lncRNAs). Using 5′ and 3′ sRNAs, the annotation of human mitochondrial was corrected and a novel ncRNA named non-coding mitochondrial RNA 1 (ncMT1) was reported for the first time in this study. We also found that most of human tRNA genes have downstream lncRNA genes as lncTRS-TGA1-1 and corrected the misunderstanding of them in previous studies. Using 5′, 3′, and intronic sRNAs, we reported for the first time that enzymatic double-stranded RNA (dsRNA) cleavage and RNA interference (RNAi) might be involved in the RNA degradation and gene expression regulation of U1 snRNA in human. We provided a different perspective on the regulation of gene expression in U1 snRNA. We also provided a novel view on cancer and virus-induced diseases, leading to find diagnostics or therapy targets from the ribonuclease III (RNase III) family and its related pathways. Our findings pave the way toward a rediscovery of dsRNA cleavage and RNAi, challenging classical theories.


title: Chapter Seven Defining Pharmacological Targets by Analysis of Virus–Host Protein Interactions

text: Abstract Viruses are obligate parasites that depend on cellular factors for replication. Pharmacological inhibition of essential viral proteins, mostly enzymes, is an effective therapeutic alternative in the absence of effective vaccines. However, this strategy commonly encounters drug resistance mechanisms that allow these pathogens to evade control. Due to the dependency on host factors for viral replication, pharmacological disruption of the host-pathogen protein–protein interactions (PPIs) is an important therapeutic alternative to block viral replication. In this review we discuss salient aspects of PPIs implicated in viral replication and advances in the development of small molecules that inhibit viral replication through antagonism of these interactions.


title: Inhibition of NF-κB activity by the porcine epidemic diarrhea virus nonstructural protein 1 for innate immune evasion

text: Abstract Porcine epidemic diarrhea virus emerged in the US is known to suppress the type I interferons response during infection. In the present study using porcine epithelial cells, we showed that PEDV inhibited both NF-κB and proinflammatory cytokines. PEDV blocked the p65 activation in infected cells and suppressed the PRD II-mediated NF-κB activity. Of the total of 22 viral proteins, nine proteins were identified as NF-κB antagonists, and nsp1 was the most potent suppressor of proinflammatory cytokines. Nsp1 interfered the phosphorylation and degradation of IκBα, and thus blocked the p65 activation. Mutational studies demonstrated the essential requirements of the conserved residues of nsp1 for NF-κB suppression. Our study showed that PEDV inhibited NF-κB activity and nsp1 was a potent NF-κB antagonist for suppression of both IFN and early production of pro-inflammatory cytokines.


title: A Single-Center Study of Viral Respiratory Tract Infections in Hospitalized Children From the Kurdistan Region of Iraq

text: Viral respiratory infections are among the most common causes of disease in humans, particularly in young children, and remain a major public health problem worldwide. For many geographic regions, there is limited epidemiological information on the main causative agents of these diseases. In this article, we investigated, in a prospective study, the viral agents leading to acute respiratory disease in children younger than 15 years of age who were admitted to the pediatric emergency unit of a major teaching hospital in Erbil City, capital of the Kurdistan region, Iraq. Nasopharyngeal samples obtained from 269 hospitalized children were analyzed for viral respiratory pathogens using the xTAG Respiratory Virus Panel Fast assay, and the data were correlated with the clinical and demographic information available for these patients. One or more respiratory virus(es) were detected in 203 out of 269 (75.5%) samples. The most frequent viruses were enterovirus/rhinovirus (n = 88; 32.7%), respiratory syncytial virus (n = 55; 20.4%), and human metapneumovirus (n = 36; 13.4%). In 42 samples (15.6%), coinfections with 2 or more respiratory viruses were detected, with enterovirus/rhinovirus, respiratory syncytial virus, human metapneumovirus, and adenovirus being identified as the most common agents in viral coinfections in these patients.


title: A novel hybrid approach to forecast crude oil futures using intraday data

text: Prediction of oil prices is an implausible task due to the multifaceted nature of oil markets. This study presents two novel hybrid models to forecast WTI and Brent crude oil prices using combinations of machine learning and nature inspired algorithms. The first approach, MARSplines-IPSO-BPNN, Multivariate Adaptive Regression Splines (MARSPlines) find the important variables that affect crude oil prices. Then, the selected variables are fed into an Improved Particle Swarm Optimization (IPSO) method to obtain the best estimates of the parameters of the Backpropagation Neural Network (BPNN). Once these parameters are obtained, the variables are fed into the BPNN model to generate the required forecasts. The second approach, MARSplines-FPA-BPNN, generates the parameters of BPNN through the Flower Pollination Algorithm (FPA). The forecasting ability of these new models is compared to certain benchmark models. The findings document that the MARSplines-FPA-BPNN model performs better than the other competitive models.


title: Spatial and temporal differentiation of COVID-19 epidemic spread in mainland China and its influencing factors

text: Abstract This paper uses the exploratory spatial data analysis and the geodetector method to analyze the spatial and temporal differentiation characteristics and the influencing factors of the COVID-19 (corona virus disease 2019) epidemic spread in mainland China based on the cumulative confirmed cases, average temperature, and socio-economic data. The results show that: (1) the epidemic spread rapidly from January 24 to February 20, 2020, and the distribution of the epidemic areas tended to be stable over time. The epidemic spread rate in Hubei province, in its surrounding, and in some economically developed cities was higher, while that in western part of China and in remote areas of central and eastern China was lower. (2) The global and local spatial correlation characteristics of the epidemic distribution present a positive correlation. Specifically, the global spatial correlation characteristics experienced a change process from agglomeration to decentralization. The local spatial correlation characteristics were mainly composed of the‘high-high’ and ‘low-low’ clustering types, and the situation of the contiguous layout was very significant. (3) The population inflow from Wuhan and the strength of economic connection were the main factors affecting the epidemic spread, together with the population distribution, transport accessibility, average temperature, and medical facilities, which affected the epidemic spread to varying degrees. (4) The detection factors interacted mainly through the mutual enhancement and nonlinear enhancement, and their influence on the epidemic spread rate exceeded that of single factors. Besides, each detection factor has an interval range that is conducive to the epidemic spread.


title: New Insights into the Roles of Metalloproteinases in Neurodegeneration and Neuroprotection

text: Proteolytic enzymes constitute around 2% of the human genome and are involved in many stages of cell development from fertilization to death (apoptosis). The identification of many novel proteases from genome‐sequencing programs has suggested them as potential new therapeutic targets. In addition, several well‐characterized metallopeptidases were recently shown to possess new biological roles in neuroinflammation and neurodegeneration. As a result of these studies, metabolism of the neurotoxic and inflammatory amyloid peptide (Aβ) is considered as a physiologically relevant process with several metallopeptidases being suggested for the role of amyloid‐degrading enzymes. These include the neprilysin (NEP) family of metalloproteinases (including its homologue endothelin‐converting enzyme), insulin‐degrading enzyme, angiotensin‐converting enzyme, plasmin, and, possibly, some other enzymes. NEP also has a role in metabolism of sensory and inflammatory neuropeptides such as tachykinins and neurokinins. The existence of natural enzymatic mechanisms for removal of amyloid peptides has extended the therapeutic avenues in Alzheimer's disease (AD) and neurodegeneration. The proteolytic events underlying AD are highly compartmentalized in the cell and formation of amyloid peptide from its precursor molecule APP (amyloid precursor protein) takes place both within intracellular compartments and in the plasma membrane, especially in lipid raft domains. Degradation of amyloid peptide by metallopeptidases can also be both intra‐ and extracellular depending on the activity of membrane‐bound enzymes and their soluble partners. Soluble forms of proteases can be secreted or released from the cell surface through the activity of “sheddases”—another group of proteolytic enzymes involved in key cellular regulatory functions. The activity of proteases involved in amyloid metabolism depends on numerous factors (e.g., genetic, environmental, age), and some conditions (e.g., hypoxia and ischemia) shift the balance of amyloid metabolism toward accumulation of higher concentrations of Aβ. In this regard, regulation of the activity of amyloid‐degrading enzymes should be considered as a viable strategy in neuroprotection.


title: Plan de contingencia para los servicios de medicina intensiva frente a la pandemia COVID-19

text: Resumen En enero de 2020 China identificó un nuevo virus de la familia de los Coronaviridae como causante de varios casos de neumonía de origen desconocido. Inicialmente confinado a la ciudad de Wuhan, se extendió posteriormente fuera de las fronteras chinas. En España el primer caso se declaró el 31 de enero de 2020. El 11 de marzo, la Organización Mundial de la Salud declaró el brote de coronavirus como pandemia. El 16 de marzo había 139 países afectados. Ante esta situación, las sociedades científicas SEMICYUC y SEEIUC han decidido la elaboración de este plan de contingencia para dar respuesta a las necesidades que conllevará esta nueva enfermedad. Se pretende estimar la magnitud del problema e identificar las necesidades asistenciales, de recursos humanos y materiales, de manera que los servicios de medicina intensiva del país tengan una herramienta que les permita una planificación óptima y realista con que responder a la pandemia. Abstract In January 2020, the Chinese authorities identified a new virus of the Coronaviridae family as the cause of several cases of pneumonia of unknown aetiology. The outbreak was initially confined to Wuhan City, but then spread outside Chinese borders. On 31 January 2020, the first case was declared in Spain. On 11 March 2020, The World Health Organization (WHO) declared the coronavirus outbreak a pandemic. On 16 March 2020, there were 139 countries affected. In this situation, the Scientific Societies SEMICYUC and SEEIUC have decided to draw up this Contingency Plan to guide the response of the Intensive Care Services. The objectives of this plan are to estimate the magnitude of the problem and identify the necessary human and material resources. This is to provide the Spanish Intensive Medicine Services with a tool to programme optimal response strategies.


docid: sbascdya

title: Stage of Gestation at Porcine Epidemic Diarrhea Virus Infection of Pregnant Swine Impacts Maternal Immunity and Lactogenic Immune Protection of Neonatal Suckling Piglets

text: During pregnancy, the maternal immune response changes dramatically over the course of gestation. This has implications for generation of lactogenic immunity and subsequent protection in suckling neonates against enteric viral infections. For example, porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus that causes acute diarrhea in neonatal piglets. Due to the high virulence of PEDV and the naïve, immature immune system of neonatal suckling piglets, passive lactogenic immunity to PEDV induced during pregnancy, via the gut-mammary gland (MG)-secretory IgA (sIgA) axis, is critical for piglet protection. However, the anti-PEDV immune response during pregnancy and stage of gestation required to optimally stimulate the gut-MG-sIgA axis is undefined. We hypothesize that there is a gestational window in which non-lethal PEDV infection of pregnant gilts influences maximum lymphocyte mucosal trafficking to the MG, resulting in optimal passive lactogenic protection in suckling piglets. To understand how the stages of gestation affect maternal immune responses to PEDV, three groups of gilts were orally infected with PEDV in the first, second or third trimester. Control (mock) gilts were inoculated with medium in the third trimester. To determine if lactogenic immunity correlated with protection, all piglets were PEDV-challenged at 3–5 days postpartum. PEDV infection of gilts at different stages of gestation significantly affected multiple maternal systemic immune parameters prepartum, including cytokines, B cells, PEDV antibodies (Abs), and PEDV antibody secreting cells (ASCs). Pregnant second trimester gilts had significantly higher levels of circulating PEDV IgA and IgG Abs and ASCs and PEDV virus neutralizing (VN) Abs post PEDV infection. Coinciding with the significantly higher PEDV Ab responses in second trimester gilts, the survival rate of their PEDV-challenged piglets was 100%, compared with 87.2, 55.9, and 5.7% for first, third, and mock litters, respectively. Additionally, piglet survival positively correlated with PEDV IgA Abs and ASCs and VN Abs in milk and PEDV IgA and IgG Abs in piglet serum. Our findings have implications for gestational timing of oral attenuated PEDV maternal vaccines, whereby PEDV intestinal infection in the second trimester optimally stimulated the gut-MG-sIgA axis resulting in 100% lactogenic immune protection in suckling piglets.


title: Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections

text: Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Through real-time RT-PCR testing, AIVs were detected in 45% of 1048 samples collected throughout the year. Detection rates ranged from 32% and 18% in duck and chicken swabs, respectively, to 75% in carcass wash water samples. Influenza A/H5N1 virus was detected in 79% of samples positive for influenza A virus and 35% of all samples collected. Sequence analysis of full-length haemagglutinin (HA) and neuraminidase (NA) genes from A/H5N1 viruses, and full-genome analysis of six representative isolates, revealed that the clade 1.1.2 reassortant virus associated with Cambodian human cases during 2013 was the only A/H5N1 virus detected during the year. However, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HA and NA genes revealed co-circulation of at least nine low pathogenic AIVs from HA1, HA2, HA3, HA4, HA6, HA7, HA9, HA10 and HA11 subtypes. Four repeated serological surveys were conducted throughout the year in a cohort of 125 poultry workers. Serological testing found an overall prevalence of 4.5% and 1.8% for antibodies to A/H5N1 and A/H9N2, respectively. Seroconversion rates of 3.7 and 0.9 cases per 1000 person-months participation were detected for A/H5N1 and A/H9N2, respectively. Peak AIV circulation was associated with the Lunar New Year festival. Knowledge of periods of increased circulation of avian influenza in markets should inform intervention measures such as market cleaning and closures to reduce risk of human infections and emergence of novel AIVs.


title: Infections nosocomiales à coronavirus humains chez le nouveau-né 1 Travail financé en partie par la Société française de pédiatrie (bourse de DEA), le ministère de la santé (PHRC 97) et le CCLIN–Ouest. A. Gagneur est boursier de la Société française de pédiatrie.

text: Résumé Les coronavirus humains sont des virus enveloppés à ARN de la famille des Coronaviridae avec deux sérogroupes identifiés : 229-E et OC-43. Ces virus possèdent le plus grand ARN viral connu. Ce génome est un ARN simple brin positif associé à une protéine phosphorylée de la nucléocapside, la protéine N. L’enveloppe des coronavirus humains contient deux ou trois glycoprotéines membranaires : S ou spike protein, M ou protéine de membrane et HE ou hémagglutine-estérase. Le rôle pathogène de ces virus est mal connu en raison des difficultés diagnostiques. Cependant la mise au point de l’immunofluorescence avec anticorps monoclonaux et des techniques d’amplification génique permet de nouvelles recherches épidémiologiques. Les coronavirus peuvent survivre jusqu’à six jours en suspension et trois heures après séchage, ce qui suggère un rôle nosocomial potentiel. Deux études prospectives réalisées dans une unité de réanimation néonatale et pédiatrique ont révélé une relation significative entre l’existence de prélèvement nasopharyngés positifs et la survenue de symptômes respiratoires. Des prélèvements positifs chez le personnel suggèrent une contamination patient-personnel ou personnel–patient. En raison de leur survie possible sur les surfaces et de l’efficacité démontrée des agents désinfectants, des mesures universelles de prévention associant lavage des mains et désinfection des surfaces peuvent être proposées. Abstract Human coronaviruses, with two known serogroups named 229-E and OC-43, are enveloped positive-stranded RNA viruses. The large RNA is surrounded by a nucleoprotein (protein N). The envelop contains 2 or 3 glycoproteins: spike protein (or protein S), matrix protein (or protein M) and a hemagglutinin (or protein HE). Their pathogen role remains unclear because their isolation is difficult. Reliable and rapid methods as immunofluorescence with monoclonal antibodies and reverse transcription-polymerase chain reaction allow new researches on epidemiology. Human coronaviruses can survive for as long as 6 days in suspension and 3 hours after drying on surfaces, suggesting that they could be a source of hospital-acquired infections. Two prospective studies conducted in a neonatal and paediatric intensive care unit demonstrated a significant association of coronavirus-positive naso-pharyngal samples with respiratory illness in hospitalised preterm neonates. Positive samples from staff suggested either a patient-to-staff or a staff-to-patient transmission. No cross-infection were observed from community-acquired respiratory-syncitial virus or influenza-infected children to neonates. Universal precautions with hand washing and surface desinfection could be proposed to prevent coronavirus transmission.


title: Nucleotide sequence comparison of the membrane protein genes of three enterotropic strains of mouse hepatitis virus

text: Abstract The nucleotide sequences of the membrane (M) protein genes and their deduced amino acid sequences of three enterotropic strains of the coronavirus mouse hepatitis virus (MHV) -Y, -RI and -DVIM were determined and compared with the previously reported sequences of two respiratory MHV strains -A59 and -JHM. The five MHV strains shared extensive nucleotide (95.2–99.0%) as well as amino acid homology (95.6–98.7%). A variable region, including a 15 nucleotide deletion unique to MHV-RI, could be identified at the 5'-terminus of the gene. This region of the M protein may be immunogenic and may contribute to the antigenic diversity of the MHV strains. Sequence relationships between the strains showed no correspondence with the primary cell tropism. This may suggest that evolution of enterotropism was not a single occurrence among different MHV strains. No sequence unique to either tropism group could be identified, indicating that the M protein of MHV probably has no part in the determination of MHV tissue tropism.


title: Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study

text: BACKGROUND: The long term adverse effects of Severe Acute Respiratory Syndrome (SARS), a viral disease, are poorly understood. METHODS: Sleep physiology, somatic and mood symptoms of 22 Toronto subjects, 21 of whom were healthcare workers, (19 females, 3 males, mean age 46.29 yrs.+/- 11.02) who remained unable to return to their former occupation (mean 19.8 months, range: 13 to 36 months following SARS) were compared to 7 healthy female subjects. Because of their clinical similarities to patients with fibromyalgia syndrome (FMS) these post-SARS subjects were similarly compared to 21 drug free female patients, (mean age 42.4 +/- 11.8 yrs.) who fulfilled criteria for fibromyalgia. RESULTS: Chronic post-SARS is characterized by persistent fatigue, diffuse myalgia, weakness, depression, and nonrestorative sleep with associated REM-related apneas/hypopneas, an elevated sleep EEG cyclical alternating pattern, and alpha EEG sleep anomaly. Post- SARS patients had symptoms of pre and post-sleep fatigue and post sleep sleepiness that were similar to the symptoms of patients with FMS, and similar to symptoms of patients with chronic fatigue syndrome. Both post-SARS and FMS groups had sleep instability as indicated by the high sleep EEG cyclical alternating pattern rate. The post-SARS group had a lower rating of the alpha EEG sleep anomaly as compared to the FMS patients. The post-SARS group also reported less pre-sleep and post-sleep musculoskeletal pain symptoms. CONCLUSIONS: The clinical and sleep features of chronic post-SARS form a syndrome of chronic fatigue, pain, weakness, depression and sleep disturbance, which overlaps with the clinical and sleep features of FMS and chronic fatigue syndrome.


title: Excess of Mortality in Adults and Elderly and Circulation of Subtypes of Influenza Virus in Southern Brazil

text: PURPOSE: In the elderly population, the influenza infection and its clinical complications are important causes of hospitalization and death, particularly, in longer-lived age. The objective of this study is to analyze the impact of influenza virus circulation on mortality in the elderly and adults, in years with different predominant virus strains. METHODS: We performed a time trend study to evaluated excess of mortality for pneumonia and influenza, respiratory disease, and all-causes in southern region of Brazil, from 2002 to 2015. After considering other models, we opted for Serfling regression. Excess of death rates per 100,000 inhabitants were analyzed in specific age groups (24–59, 60–69, 70–79, ≥80 years) and by year of occurrence. Mortality information were taken from Brazilian Mortality Information System and etiological data were accessed in Sentinel Virological Surveillance database, getting the weekly positivity of the immunofluorescence tests for influenza A (H1N1, H3N2), and B. RESULTS: In southern Brazil, there is an evident seasonal pattern of all death outcomes among different age groups in the dry and cold season (April–September). The highest excess mortality rates occurs among older, particularly in years of circulation of influenza AH3N2, especially among people ≥80 years, in 2003 and 2007—years of great severity of influenza activity. After 2009, with the introduction of the pandemic influenza AH1N1, we observed a lower impact on the mortality of the elderly compared to <60 years. DISCUSSION: A cross reactivity antibody response from past exposure probably provided protection against disease in the elderly. Despite not controlling for comorbidities, climate, and vaccination, for the >70 years, ratio of respiratory diseases excess mortality rates between AH1N1 (2009) and severe year of H3N2 (2007) shows protection in the pandemic year and great vulnerability during AH3N2 virus predominance. CONCLUSION: The reduced immune response to infection, and to vaccination, and presence of comorbidities recommend a special attention to this age group in Brazil. Besides medical assistance, the timeliness of vaccine campaigns, its composition, and etiological surveillance of respiratory diseases are some of the preventive and public health measures.


title: Different Types of Door-Opening Motions as Contributing Factors to Containment Failures in Hospital Isolation Rooms

text: Hospital isolation rooms are vital for the containment (when under negative pressure) of patients with, or the protection (when under positive pressure) of patients, from airborne infectious agents. Such facilities were essential for the management of highly contagious patients during the 2003 severe acute respiratory syndrome (SARS) outbreaks and the more recent 2009 A/H1N1 influenza pandemic. Many different types of door designs are used in the construction of such isolation rooms, which may be related to the space available and affordability. Using colored food dye as a tracer, the qualitative effects of door-opening motions on the dissemination of potentially contaminated air into and out of a single isolation room were visualized and filmed using Reynolds-number-equivalent, small-scale, water-tank models fitted with programmable door-opening and moving human figure motions. Careful scaling considerations involved in the design and construction of these water-tank models enabled these results to be accurately extrapolated to the full-scale situation. Four simple types of door design were tested: variable speed single and double, sliding and hinged doors, in combination with the moving human figure. The resulting video footage was edited, synchronized and presented in a series of split-screen formats. From these experiments, it is clear that double-hinged doors pose the greatest risk of leakage into or out of the room, followed by (in order of decreasing risk) single-hinged, double-sliding and single-sliding doors. The relative effect of the moving human figure on spreading any potential contamination was greatest with the sliding doors, as the bulk airflows induced were large relative to those resulting from these door-opening motions. However, with the hinged doors, the airflows induced by these door-opening motions were significantly greater. Further experiments involving a simulated ventilated environment are required, but from these findings alone, it appears that sliding-doors are far more effective for hospital isolation room containment.


title: Identification of a novel nidovirus in an outbreak of fatal respiratory disease in ball pythons (Python regius)

text: BACKGROUND: Respiratory infections are important causes of morbidity and mortality in reptiles; however, the causative agents are only infrequently identified. FINDINGS: Pneumonia, tracheitis and esophagitis were reported in a collection of ball pythons (Python regius). Eight of 12 snakes had evidence of bacterial pneumonia. High-throughput sequencing of total extracted nucleic acids from lung, esophagus and spleen revealed a novel nidovirus. PCR indicated the presence of viral RNA in lung, trachea, esophagus, liver, and spleen. In situ hybridization confirmed the presence of intracellular, intracytoplasmic viral nucleic acids in the lungs of infected snakes. Phylogenetic analysis based on a 1,136 amino acid segment of the polyprotein suggests that this virus may represent a new species in the subfamily Torovirinae. CONCLUSIONS: This report of a novel nidovirus in ball pythons may provide insight into the pathogenesis of respiratory disease in this species and enhances our knowledge of the diversity of nidoviruses.


title: A G-quadruplex-binding macrodomain within the “SARS-unique domain” is essential for the activity of the SARS-coronavirus replication–transcription complex

text: Abstract The multi-domain non-structural protein 3 of SARS-coronavirus is a component of the viral replication/transcription complex (RTC). Among other domains, it contains three sequentially arranged macrodomains: the X domain and subdomains SUD-N as well as SUD-M within the “SARS-unique domain”. The X domain was proposed to be an ADP-ribose-1”-phosphatase or a poly(ADP-ribose)-binding protein, whereas SUD-NM binds oligo(G)-nucleotides capable of forming G-quadruplexes. Here, we describe the application of a reverse genetic approach to assess the importance of these macrodomains for the activity of the SARS-CoV RTC. To this end, Renilla luciferase-encoding SARS-CoV replicons with selectively deleted macrodomains were constructed and their ability to modulate the RTC activity was examined. While the SUD-N and the X domains were found to be dispensable, the SUD-M domain was crucial for viral genome replication/transcription. Moreover, alanine replacement of charged amino-acid residues of the SUD-M domain, which are likely involved in G-quadruplex-binding, caused abrogation of RTC activity.


title: Knowledge Level and Hand Hygiene Practice of Nepalese Immigrants and Their Host Country Population: A Comparative Study

text: Nepali people are one of the ethnic minority immigrants of Hong Kong. This epidemiological investigation aims to determine and compare the knowledge level and hand hygiene (HH) behaviour of the Nepali people and the population of their host country (i.e., native Chinese population of Hong Kong). A total of 1008 questionnaires were collected via an online platform. The overall knowledge level of the native population towards HH was considerably higher than that of the Nepali respondents. Lower levels of knowledge in young and older people were noted. Reduced HH knowledge was also observed in people with low educational level or with comorbid illness(es). Significant differences between groups were noted in the self-reported hand washing behaviours. Regarding hand drying, more Nepalese than native Chinese respondents always/sometimes dried their hands on their clothing irrespective whether after performing handwashing in public washrooms or at home. Misconceptions and suboptimal practices on HH were prevalent in the two populations. The findings of this comparative study offer valuable information for the development of culturally sensitive health educational programs to enhance HH practices for the ethnic minorities and native Chinese population.


docid: eiulendi

title: The broad-spectrum antiviral recommendations for drug discovery against COVID-19

text: Despite to outbreaks of highly pathogenic beta and alpha coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus, the newly emerged 2019 coronavirus (COVID-19) is considered as a lethal zoonotic virus due to its deadly respiratory syndrome and high mortality rate among the human. Globally, more than 3,517,345 cases have been confirmed with 243,401 deaths due to Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19. The antiviral drug discovery activity is required to control the persistence of COVID-19 circulation and the potential of the future emergence of coronavirus. However, the present review aims to highlight the important antiviral approaches, including interferons, ribavirin, mycophenolic acids, ritonavir, lopinavir, inhibitors, and monoclonal antibodies (mAbs) to provoke the nonstructural proteins and deactivate the structural and essential host elements of the virus to control and treat the infection of COVID-19 by inhibiting the viral entry, viral RNA replication and suppressing the viral protein expression. Moreover, the present review investigates the epidemiology, diagnosis, structure, and replication of COVID-19 for better understanding. It is recommended that these proteases, inhibitors, and antibodies could be a good therapeutic option in drug discovery to control the newly emerged coronavirus. HIGHLIGHTS: COVID-19 has more than 79.5% identical sequence to SARS-CoV and a 96% identical sequence of the whole genome of bat coronaviruses. Acute respiratory distress syndrome (ARDS), renal failure, and septic shock are the possible clinical symptoms associated with COVID-19. Different antivirals, including interferons, ribavirin, lopinavir, and monoclonal antibodies (mAbs) could be the potent therapeutic agents against COVID-19. The initial clinical trials on hydroquinone in combination with azithromycin showed an admirable result in the reduction of COVID-19. The overexpression of inflammation response, cytokine dysregulation, and induction of apoptosis could be an well-organized factors to reduce the pathogenicity of COVID-19.


title: COVID-19 and airline employment: Insights from historical uncertainty shocks to the industry

text: Abstract The purpose of this paper is to analyze the effects of uncertainty shocks on airline employment in the light of the current global pandemic. The airline industry has faced many threats throughout history, but none quite as rapid and severe as the one posed by the spread of COVID-19. One constant during uncertainty shocks and industry downturns is that airline labor bears the brunt of the decline. As the industry reduces capacity amid the increase in travel restrictions, the post-stimulus impacts to airline labor are not known. Using time series analysis, the dynamics of historical uncertainty shocks to the industry are examined. During periods of uncertainty shocks, the estimated job loss is nearly 7% of the airline workforce with an upper bound of over 13%. Major airline employment is most impacted, while low-cost and regional airline employment is least impacted. The hardest hit employees are ones related to passenger handling and flight operations, while management employees fair slightly better during these uncertain periods. Further, recovery following uncertainty shocks is estimated to take between 4 and 6 years. Overall, the labor impacts to the airline industry from uncertainty events are substantial and provide insight into the expected industry job loss from COVID-19.


title: The role of respiratory tract infections and the microbiome in the development of asthma: A narrative review

text: Asthma is a common disease in childhood, and might predispose for chronic obstructive respiratory morbidity in adolescence and adulthood. Various early‐life risk factors might influence the risk of wheezing, asthma, and lower lung function in childhood. Cohort studies demonstrated that lower respiratory tract infections in the first years of life are associated with an increased risk of wheezing and asthma, while the association with lung function is less clear. Additionally, the gut and airway microbiome might influence the risk of wheezing and asthma. The interaction between respiratory tract infections and the microbiome complicates studies of their associations with wheezing, asthma, and lung function. Furthermore, the causality behind these observations is still unclear, and several other factors such as genetic susceptibility and the immune system might be of importance. This review is focused on the association of early‐life respiratory tract infections and the microbiome with wheezing, asthma, and lung function, it is possible influencing factors and perspectives for future studies.


title: Association between ambient temperature and COVID-19 infection in 122 cities from China

text: Abstract Background Coronavirus disease 2019 (COVID-19) has become a severe public health problem globally. Both epidemiological and laboratory studies have shown that ambient temperature could affect the transmission and survival of coronaviruses. This study aimed to determine whether the temperature is an essential factor in the infection caused by this novel coronavirus. Methods Daily confirmed cases and meteorological factors in 122 cities were collected between January 23, 2020, to February 29, 2020. A generalized additive model (GAM) was applied to explore the nonlinear relationship between mean temperature and COVID-19 confirmed cases. We also used a piecewise linear regression to determine the relationship in detail. Results The exposure-response curves suggested that the relationship between mean temperature and COVID-19 confirmed cases was approximately linear in the range of <3 °C and became flat above 3 °C. When mean temperature (lag0–14) was below 3 °C, each 1 °C rise was associated with a 4.861% (95% CI: 3.209–6.513) increase in the daily number of COVID-19 confirmed cases. These findings were robust in our sensitivity analyses. Conclusions Our results indicate that mean temperature has a positive linear relationship with the number of COVID-19 cases with a threshold of 3 °C. There is no evidence supporting that case counts of COVID-19 could decline when the weather becomes warmer, which provides useful implications for policymakers and the public.


title: Differentiation of feline coronavirus type I and II infections by virus neutralization test

text: Abstract Feline coronavirus (FCoV) is divided into two types I and II, based on their growth in vitro and antigenicity. In this study, virus neutralization (VN) test was applied for type differentiation of FCoV infections. Sera of cats which were clinically and serologically diagnosed as feline infectious peritonitis (FIP) possessed significantly higher VN titers to type I FCoV, and sera from cats experimentally infected with FIPV type II had high VN titers to type II but not type I viruses. A total of 79 cat sera collected in the years between 2004 and 2005 were examined to evaluate seroprevalence by the VN test, showing the following results: (1) 50 cats (63.3%) were sero-positive to FCoV; (2) of the 50 FCoV positive cat serum samples, 49 (98%) showed significantly higher titers to type I virus and only one (2%) for type II virus. These results indicate that the VN test described here can be used for serological differentiation of FCoV infections of cats, and that FCoV type I is a dominant type in recent years of Japan.


title: Differentiation of a Vero cell adapted porcine epidemic diarrhea virus from Korean field strains by restriction fragment length polymorphism analysis of ORF 3

text: A porcine epidemic diarrhea virus (PEDV) designated DR13 was isolated in Vero cells and serially passaged by level 100. The virus was titrated at regular intervals of the passage level. Open reading frame (ORF) 3 sequences of the virus at passage levels 20, 40, 60, 80, and 100 were aligned and compared using a computer software program. Suitability of the restriction fragment length polymorphism (RFLP) analysis for differentiating the virus from other Korean field strains was investigated. The DR13 field isolate was successively adapted in Vero cells as observed through polymerase chain reaction (PCR) and titration of the virus. RFLP analysis identified change in cleavage sites of HindIII and Xho II from passage levels 75 and 90, respectively; these RFLP patterns of ORF 3 differentiated the Vero cell-adapted virus from its parent strain, DR13, and 12 other strains of PEDV studied. The cell adapted DR13 was tested for its pathogenicity and immunogenicity in piglets and pregnant sows. The results indicated that cell adapted DR13 revealed reduced pathogenicity and induced protective immune response in pigs. Differentiation between highly Vero cell-adapted virus and wild-type virus could be the marker of adaptation to cell culture and a valuable tool for epidemiologic studies of PEDV infections. The results of this study supported that the cell attenuated virus could be applied as a marker vaccine candidate against PEDV infection.


title: Peptide inhibition of human cytomegalovirus infection

text: BACKGROUND: Human cytomegalovirus (HCMV) is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV)- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB), a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. RESULTS: Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS), several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF) were infected with the Towne-GFP strain of HCMV (0.5 MOI), preincubated with peptides at a range of concentrations (78 nm to 100 μM), and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100 μM and 50 μM, respectively, and 60% at a concentration of 2.5 μM. While peptides 264-291 and 297-315, individually failed to inhibit viral infection, when combined, they showed 67% inhibition of HCMV infection at a concentration of 0.125 μM each. CONCLUSIONS: Peptides designed to target putative fusogenic domains of gB provide a basis for the development of novel therapeutics that prevent HCMV infection.


The Biology of the Interferon System


title: A compendium answering 150 questions on COVID‐19 and SARS‐CoV‐2

text: In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID‐19). This disease, caused by the severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2), has developed into a pandemic. To date it has resulted in ~6.5 million confirmed cases and caused almost 400,000 related deaths worldwide. Unequivocally, the COVID‐19 pandemic is the gravest health and socio‐economic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence‐based medical advice on SARS‐CoV‐2 and COVID‐19. Although the majority of the patients show a very mild, self‐limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID‐19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a “cytokine storm” leading to acute respiratory distress syndrome, endothelitis, thrombo‐embolic complications and multiorgan failure. The epidemiologic features of COVID‐19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID‐19‐related topics should be based on more coordinated high‐quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS‐CoV‐2, COVID‐19 and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development and epidemiology. Over 140 questions were answered by experts in the field providing a comprehensive and practical overview of COVID‐19 and allergic disease.


title: Application of Aptamer Based Biosensors for Detection of Pathogenic Microorganisms

text: Abstract Aptamer is a kind of synthetic oligonucleotides discriminated by in vitro screening and systematic evolution of exponential enrichment technology (SELEX), which can bind to certain targets (small molecules, proteins, or even entire cells) with extremely high specificity. Owing to the advantages of simple preparation, easy modification and good stability, aptamers have been used to construct biosensors for the detection of pathogenic microorganisms. This paper presents the latest advances in SELEX for screening aptamers for pathogenic microorganisms, demonstrates some reported aptamers for pathogenic microorganisms (protozoa, viruses, bacteria), and reviews aptamer based biosensors for detection of pathogenic microorganisms. Finally, the new trends in aptamer based biosensors for detection of pathogenic microorganisms are also discussed.


title: Public health microbiology in Germany: 20 years of national reference centers and consultant laboratories

text: Abstract In 1995, in agreement with the German Federal Ministry of Health, the Robert Koch Institute established a public health microbiology system consisting of national reference centers (NRCs) and consultant laboratories (CLs). The goal was to improve the efficiency of infection protection by advising the authorities on possible measures and to supplement infectious disease surveillance by monitoring selected pathogens that have high public health relevance. Currently, there are 19 NRCs and 40 CLs, each appointed for three years. In 2009, an additional system of national networks of NRCs and CLs was set up in order to enhance effectiveness and cooperation within the national reference laboratory system. The aim of these networks was to advance exchange in diagnostic methods and prevention concepts among reference laboratories and to develop geographic coverage of services. In the last two decades, the German public health laboratory reference system coped with all major infectious disease challenges. The European Union and the European Centre for Disease Prevention and Control (ECDC) are considering implementing a European public health microbiology reference laboratory system. The German reference laboratory system should be well prepared to participate actively in this upcoming endeavor.


What is the time-scale of hantavirus evolution?


Transesophageal echocardiography remains essential and safe during prone ventilation for hemodynamic monitoring of COVID-19 patients.


docid: zreerqqv

title: In Response to Isolated Anosmia and Ageusia in COVID‐19 With Spontaneous Recovery


title: Clinical and Autoimmune Characteristics of Severe and Critical Cases of COVID‐19

text: In this study we report on the clinical and autoimmune characteristics of severe and critical novel coronavirus pneumonia caused by severe acute respiratory syndrome‒associated coronavirus 2 (SARS‐CoV‐2). The clinical, autoimmune, and laboratory characteristics of 21 patients who had laboratory‐confirmed severe and critical cases of coronavirus disease 2019 (COVID‐19) from the intensive care unit of the Huangshi Central Hospital, Hubei Province, China, were investigated. A total of 21 patients (13 men and 8 women), including 8 (38.1%) severe cases and 13 (61.9%) critical cases, were enrolled. Cough (90.5%) and fever (81.0%) were the dominant symptoms, and most patients (76.2%) had at least one coexisting disorder on admission. The most common characteristics on chest computed tomography were ground‐glass opacity (100%) and bilateral patchy shadowing (76.2%). The most common findings on laboratory measurement were lymphocytopenia (85.7%) and elevated levels of C‐reactive protein (94.7%) and interleukin‐6 (89.5%). The prevalence of anti‒52 kDa SSA/Ro antibody, anti‒60 kDa SSA/Ro antibody, and antinuclear antibody was 20%, 25%, and 50%, respectively. We also retrospectively analyzed the clinical and laboratory data from 21 severe and critical cases of COVID‐19. Autoimmune phenomena exist in COVID‐19 subjects, and the present results provide the rationale for a strategy of preventing immune dysfunction and optimal immunosuppressive therapy.


title: A Global Respiratory Perspective on the COVID-19 Pandemic: Commentary and Action Proposals

text: This paper offers practical and feasible actions to be implemented at patient, health care provider and community level to combat COVID-19 while attending, maintaining and strengthening ongoing health management in people with lung diseases.


title: Intracellular synthesis and processing of the structural glycoproteins of turkey enteric coronavirus

text: Pulse labeling of cells with [(35)S]methionine or [(3)H]glucosamine at different times after infection, followed by SDS-PAGE and Western immunoblotting analysis using rabbit anti-TCV hyperimmune serum, was used to resolve and identify TCV-induced intracellular proteins. The viral structural proteins (gp200, gp140/gp66, gp100/gp120, p52, and gp24/p20) were detected in radiolabeled cell extracts by 9 to 12 hours post-infection, as well as two possible non-structural proteins with apparent mol.wts. of 36,000 and 32,000. The predominant 52,000 nucleocapsid protein could be detected in cell lysates as soon as 6 to 8 hours after infection; it was initially resolved as a complex of 3 closely migrating species with mol.wts. ranging from 46,000 to 52,000. Pulse-chase and immunoprecipitation experiments indicated that gp200 arose from a putative precursor with mol.wt. of 150,000 to 170,000, that underwent glycosylation. Proteolytic cleavage of gp200, in turn, probably yielded the gp100 and gp120 species. The unique TCV hemagglutinin protein originated from a primary precursor with mol.wt. of 60,000, which underwent rapid dimerization by disulfide bond formation and glycosylation to yield gp140. The peplomeric and matrix proteins were both shown to be N-glycosylated, as indicated by their sensitivity to tunicamycin (TM) and their resistance to sodium monensin (SM). In the presence of TM, proteins with mol.wts. of 90,000, 120–130,000, and 150,000 accumulated in TCV-infected cells rather than peplomeric glycoproteins, and the matrix protein E1 was only detected in its unglycosylated form. The addition of TM to the culture medium interfered with the maturation of progeny viral particles, as suggested by the absence of peplomers at the surface of the intravacuolar and extracellular virions, and the accumulation of amorphous material not found in the absence of the glycosylation inhibitor. High yields of virus replication were obtained, in the presence of SM, even at concentrations which greatly affected the cellular functions.


Maternal postnatal health during the COVID-19 pandemic: vigilance is needed


title: Seasonal Allergy and Seasonal Decrements in Athletic Performance

text: Allergic diseases are common in all age groups and locations around the world. In the United States, allergic diseases affect 20 to 40 million people annually, including 10% to 30% of adults and close to 40% of children. An estimated 15 million people in the United States have been diagnosed as having asthma, with this number on the rise. Concomitant asthma affects 67% of patients who have allergic rhinitis. As a result of the increase in ventilation during exercise, athletes in particular experience significant symptoms of allergy triggered by exposure to aeroallergens. The allergic response causes nasal and conjunctival congestion, tearing, breathing difficulties, pruritus, fatigue, and mood changes, which affect athletic performance. Systemic symptoms of anaphylaxis from allergy, although rare, can be life threatening. Several decades ago it was inconceivable that an athlete who had asthma could perform competitively, let alone win Olympic gold medals. Today, with proper diagnosis, education, and optimal therapeutic management, the allergic athlete can achieve great strides in all sports endeavors. To avoid seasonal allergic flares and maximize performance, the physician providing care for an athlete who has seasonal allergies must be aware of the climatic patterns of aeroallergen expression, and adjust exercise and pharmacologic regimens accordingly. This article summarizes the effects of allergic disease on exercise and highlights the challenges that seasonal allergy place on athletic performance. Doping considerations grant additional complexity to this issue and underscore the need for a competent, skillful, informed, and ethical approach to treating seasonal allergy in the competitive athlete.


Safe Reintroduction of Cardiovascular Services during the COVID-19 Pandemic: Guidance from North American Societies