title: Lignes directrices quant à la prise en charge des patientes en obstétrique chez lesquelles la présence du syndrome respiratoire aigu sévère (SRAS) est soupçonnée ou probable, et des nouveau-nés issus de ces patientes

text: OBJECTIF: Le présent document résume notre expérience limitée quant à la présence du SRAS pendant la grossesse et suggère des lignes directrices quant à sa prise en charge. ISSUES: Les exposés de cas issus d’Asie laissent entendre que les issues maternelles et fœtales sont aggravées par la présence du SRAS pendant la grossesse. RÉSULTATS: Des recherches ont été menées dans Medline afin d’en tirer les articles pertinents publiés en anglais entre 2000 et 2007. Des exposés de cas ont été analysés et nous avons sollicité l’opinion de spécialistes. VALEURS: Les recommandations ont été formulées conformément aux lignes directrices élaborées par le Groupe d’étude canadien sur les soins de santé préventifs. COMMANDITAIRE: La Société des obstétriciens et gynécologues du Canada. RECOMMANDATIONS: 1. Tous les hôpitaux devraient mettre en œuvre des systèmes de prévention des infections, afin de s’assurer que des alertes au sujet des modifications que connaissent les facteurs de risque d’exposition au SRAS ou à d’autres maladies transmissibles potentiellement graves sont communiquées sans tarder aux unités cliniques, y compris l’unité de travail et d’accouchement. (III-C); 2. En présence d’une éclosion de SRAS, toutes les patientes enceintes évaluées ou admises à l’hôpital devraient faire l’objet d’un dépistage des symptômes et des facteurs de risque du SRAS. (III-C); 3. À leur arrivée au sein de l’unité de triage quant au travail, les patientes enceintes chez lesquelles la présence du SRAS est soupçonnée et probable devraient être placées dans une salle d’isolement dotée d’un système de ventilation à pression négative comptant au moins six renouvellements d’air à l’heure. Toutes les unités de travail et d’accouchement offrant des soins à des patientes chez lesquelles la présence du SRAS est soupçonnée et probable devraient disposer d’au moins une salle dans laquelle ces patientes peuvent connaître leur travail et leur accouchement en toute sûreté, et ce, malgré la nécessité d’assurer un isolement aérogène. (III-C); 4. Dans la mesure du possible, le travail et l’accouchement (y compris l’accouchement opératoire ou la césarienne) devraient être pris en charge, dans une salle d’isolement désignée dotée d’un système de ventilation à pression négative, par du personnel désigné disposant d’une tenue de protection et d’une formation spécialisée en prévention des infections. (III-C); 5. Tant l’anesthésie régionale que générale peuvent s’avérer adéquates pour l’accouchement des patientes atteintes du SRAS. (III-C); 6. Les nouveau-nés issus de mères atteintes du SRAS devraient être isolés au sein d’une unité désignée jusqu’à ce que leur état ait été satisfaisant pendant 10 jours ou jusqu’à ce que la période d’isolement de la mère ait pris fin. La mère ne devrait pas allaiter pendant cette période. (III-C); 7. Une équipe multidisciplinaire (comprenant des obstétriciens, des infirmières, des pédiatres, des spécialistes de la prévention des infections, des inhalothérapeutes et des anesthésiologistes) devrait être nommée au sein de chaque unité et être responsable de l’organisation et de la mise en œuvre des protocoles de prise en charge du SRAS de l’unité. (III-C); 8. Le personnel offrant des soins aux patientes enceintes atteintes du SRAS ne devraient pas offrir leurs services aux autres patientes enceintes. Le personnel offrant des soins aux patientes enceintes atteintes du SRAS devraient activement faire l’objet d’une surveillance visant la fièvre et d’autres symptômes du SRAS. Ces personnes ne devraient pas travailler en présence de tout symptôme du SRAS se manifestant dans les 10 jours suivant une exposition à un patient atteint du SRAS. (III-C); 9. Tous les professionnels des soins de santé, les résidents et les membres du personnel de soutien devraient bénéficier d’une formation sur la prise en charge et le confinement des infections afin de prévenir la propagation du virus du SRAS. (III-A); 10. Les autorités sanitaires régionales, conjointement avec le personnel hospitalier, devraient envisager la désignation d’établissements ou d’unités de soins de santé particulières (y compris des centres de soins primaires, secondaires ou tertiaires) en ce qui concerne l’offre de soins aux patients atteints du SRAS ou de maladies semblables. (III-A)


title: Preliminary considerations regarding the risk of COVID-19 and disease severity in chronic gastrointestinal conditions

text: The novel RNA betacoronavirus SARS-CoV-2 is driving great efforts in clinical and basic research and several studies of the epidemiology, risk factors, clinical and virological features of this infection are already available. However COVID-19 is a totally new pathological entity, and many gray areas regarding associated diseases still need to be elucidated, especially in the group of patients who suffer from preexistent gastrointestinal disease. The aim of this review is to summarize the published data on the correlation between chronic gastrointestinal disorders and COVID-19.


title: Computational evaluation of the reactivity and pharmaceutical potential of an organic amine: A DFT, molecular dynamics simulations and molecular docking approach

text: Abstract 2-[N-(carboxymethyl)anilino] acetic acid (PIDAA) molecule has been spectroscopically characterized and computationally investigated for its fundamental reactive properties by a combination of density functional theory (DFT) calculations, molecular dynamics (MD) simulations and molecular docking procedure. A comparison drawn between the simulated and experimentally attained spectra by FT-Raman and FT-IR showed concurrence. The natural bond orbital (NBO) analysis enabled in comprehending the stability and charge delocalization in the title molecule. The first hyperpolarizability which is an important parameter for future studies of nonlinear optics (NLO) was calculated to check the potential of the molecule to be an NLO material. Besides, frontier molecular orbitals (FMO), electron localization function (ELF) and localized orbital locator (LOL) analysis were performed. Energy gap (ΔE), electronegativity (χ), chemical potential (μ), global hardness (η), softness (S), Mulliken population analysis on atomic charges and thermodynamic properties of the title compound at different temperatures have been calculated. The local reactive properties of PIDAA have been addressed by MEP and ALIE surfaces, together with bond dissociation energy for hydrogen abstraction (H-BDE). MD simulations have been used in order to identify atoms with pronounced interactions with water molecules. The pharmaceutical potential of PIDAA has been considered by the analysis of drug likeness parameters and molecular docking procedure. The biological activity of the molecule in terms of molecular docking has been analyzed theoretically for the treatment of SARS and minimum binding energy calculated. The Ramachandran plot was used to check the stereochemistry of the protein structure. In addition, a comparison of the physiochemical parameters of PIDAA and commercially available drugs (Yu et al., 2004; Tan et al., 2004; Elshabrawy et al., 2014; Chu et al., 2004; Gopal Samy and Xavier, 2015) were carried out.


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title: Genomic characterisation of the severe acute respiratory syndrome coronavirus of Amoy Gardens outbreak in Hong Kong

text: Severe acute respiratory syndrome (SARS) is a global health concern. In Hong Kong, two major outbreaks, one hospital based and the other in the Amoy Gardens apartments, were identified. The frequency of diarrhoea, admission to intensive care, and mortality differed significantly between the two outbreaks. We did genomic sequencing for viral isolates from five Amoy Gardens patients. The virus sequence was identical in four of these five patients. The sequence data from one hospital case and the four identical community cases had only three nucleotide differences. Alterations in the SARS coronavirus genome are unlikely to have caused the distinctive clinical features of the Amoy Gardens patients, and these results highlight the importance of non-viral genomic factors in this outbreak.


title: Rhinovirus-induced first wheezing episode predicts atopic but not nonatopic asthma at school age

text: Background Persistent childhood asthma is mainly atopy driven. However, limited data exist on the risk factors for childhood asthma phenotypes. Objective We sought to identify risk factors at the first severe wheezing episode for current asthma 7 years later and separately for atopic and nonatopic asthma. Methods One hundred twenty-seven steroid-naive children with the first severe wheezing episode (90% hospitalized/10% emergency department treated) were followed for 7 years. The primary outcome was current asthma at age 8 years, which was also analyzed separately as atopic and nonatopic asthma. Risk factors, including sensitization, viral cause, and other main asthma risk factors, were analyzed. Results At study entry, median age was 11 months (interquartile range, 6-16 months); 17% were sensitized, and 98% were virus positive. Current asthma (n = 37) at 8 years was divided into atopic (n = 19) and nonatopic (n = 18) asthma. The risk factors for current atopic asthma at study entry were sensitization (adjusted odds ratio [OR], 12; P < .001), eczema (adjusted OR, 4.8; P = .014), and wheezing with rhinovirus (adjusted OR, 5.0; P = .035). The risk factors for nonatopic asthma were the first severe respiratory syncytial virus/rhinovirus–negative wheezing episode (adjusted OR, 8.0; P = .001), first wheezing episode at age less than 12 months (adjusted OR, 7.3; P = .007), and parental smoking (adjusted OR, 3.8; P = .028). Conclusions The data suggest diverse asthma phenotypes and mechanisms that can be predicted by using simple clinical markers at the time of the first severe wheezing episode. These findings are important for designing early intervention strategies for secondary prevention of asthma.


OBJECTIVE: Coronavirus disease 2019 (COVID-19) has raised concern around the world as an epidemic or pandemic. As data on COVID-19 has grown, it has become clear that older adults have a disproportionately high rate of death from COVID-19. This study describes the early clinical characteristics of COVID-19 in patients with more than 80 years of age. METHODS: Epidemiological, clinical, laboratory, radiological, and treatment data from 17 patients diagnosed with COVID-19 between January 20 and February 20, 2020 were collected and analyzed retrospectively. Treatment outcomes among subgroups of patients with non-severe and severe symptoms of COVID-19 were compared. RESULTS: Of the 17 hospitalized patients with COVID-19, the median age was 88.0 years (interquartile range, 86.6–90.0 years; range, 80.0–100.0 years) and 12 (70.6%) were men. The age distribution of patients was not significantly different between non-severe group and severe group. All patients had chronic pre-existing conditions. Hypertension and cardiovascular diseases were the most common chronic conditions in both subgroups. The most common symptoms at the onset of COVID-19 were fever (n = 13; 76.5%), fatigue (n = 11; 64.7%), and cough (n = 5; 29.4%). Lymphopenia was observed in all patients, and lymphopenia was significantly more severe in the severe group than that in non-severe group (0.4 ×10(9)/L vs 1.2 ×10(9)/L, P = 0.014). The level of serum creatinine was higher in the severe group than in the non-severe group (99.0 μmol/L vs 62.5 μmol/L, P = 0.038). The most common features of chest computed tomography (CT) images were nodular foci in 10 (58.8%) patients and pleural thickening in 7 (41.2%) patients. All patients received antiviral therapy, while some patients also received intravenous antibiotics therapy (76.5%), Chinese medicinal preparation therapy (Lianhuaqingwen capsule, 64.7%), corticosteroids (35.3%) or immunoglobin (29.4%). Eight patients (47.1%) were transferred to the intensive care unit because of complications. Ten patients (58.8%) received intranasal oxygen, while 3 (17.6%) received non-invasive mechanical ventilation, and 4 (23.5%) received high-flow oxygen. As of June 20, 7 (41.2%) patients had been discharged and 10 (58.8% of this cohort, 77.8% of severe patients) had died. CONCLUSION: The mortality of patients aged 80 years and older with severe COVID-19 symptoms was high. Lymphopenia was a characteristic laboratory result in these patients, and the severity of lymphopenia was indicative of the severity of COVID-19. However, the majority of patients with COVID-19 in this age cohort had atypical symptoms, and early diagnosis depends on prompt use of a viral nucleic acid test. Please cite this article as: Dang JZ, Zhu GY, Yang YJ, Zheng F. Clinical characteristics of coronavirus disease 2019 in patients aged 80 years and older. J Integr Med. 2020; Epub ahead of print.


title: Short-Sighted Virus Evolution and a Germline Hypothesis for Chronic Viral Infections

text: With extremely short generation times and high mutability, many viruses can rapidly evolve and adapt to changing environments. This ability is generally beneficial to viruses as it allows them to evade host immune responses, evolve new behaviours, and exploit ecological niches. However, natural selection typically generates adaptation in response to the immediate selection pressures that a virus experiences in its current host. Consequently, we argue that some viruses, particularly those characterised by long durations of infection and ongoing replication, may be susceptible to short-sighted evolution, whereby a virus’ adaptation to its current host will be detrimental to its onward transmission within the host population. Here we outline the concept of short-sighted viral evolution and provide examples of how it may negatively impact viral transmission among hosts. We also propose that viruses that are vulnerable to short-sighted evolution may exhibit strategies that minimise its effects. We speculate on the various mechanisms by which this may be achieved, including viral life history strategies that result in low rates of within-host evolution, or the establishment of a ‘germline’ lineage of viruses that avoids short-sighted evolution. These concepts provide a new perspective on the way in which some viruses have been able to establish and maintain global pandemics.


title: Selection for 3′ end triplets for polymerase chain reaction primers

text: Abstract The 3′ end of a primer is a key component of PCR primer design. Many recommendations for the composition and sequence of the 3′ end have been suggested based on theoretical considerations, but have not been verified experimentally. We analyzed 3′ end triplets of PCR primer sequences obtained from refereed journal articles, to test those recommendations and to make empirical recommendations for primer design. The frequencies of the 64 possible 3′end triplets among 2137 PCR primers from the VirOligo database were not uniformly distributed. From the analysis, we found that unfavored and preferred 3′ end triplets existed, and that the apparent preferences were not due to base compositions in viral genome sequences. Comparison of the sequences preferred by practitioners to those recommended, suggested that no single recommendation is entirely satisfactory. We suggest that recommendations be replaced with a scoring system incorporating empirical frequencies such as those reported here.


title: Knowledge, attitudes, and practices of emergency department staff towards disaster and emergency preparedness at tertiary health care hospital in central Saudi Arabia

text: OBJECTIVES: To assess the knowledge, practices, and attitudes regarding disaster and emergency preparedness among Emergency Department (ED) staff. METHODS: This cross-sectional study was conducted at Tertiary health care hospital in central Riyadh, Kingdom of Saudi Arabia. A self-administered survey was utilized to collect data from ED physicians and nurses. The questionnaire was divided into 5 sections viz; demographics, knowledge about disaster management and preparedness, attitudes about disaster planning, current role and practices, and familiarity towards emergency. RESULTS: A 189 participants have completed the questionnaire. Two-third of the participants were below 30 years, and more than 85% were female. One hundred and eleven (58.7%) had a clinical experience of more than 5 years, while 78 (41.3%) participants had more than 3 years of clinical service at the Tertiary care hospital in Riyadh, Kingdom of Saudi Arabia. Correct responses of knowledge towards disaster and emergency preparedness score was 6.2±2.5. Participants with more than 5-years of experience had a statistically significant (p=0.009) knowledge scale score for disaster and emergency preparedness. Overall, 186 (98.4%) patients believed that training is necessary for all healthcare workers. Approximately 153 (81%) participants reported the conduct of disaster drill at their hospital. The mean score (Mean±SD) for the overall familiarity of the study participants with emergency preparedness information questionnaire (EPIQ) scale was 3.2±1.3. CONCLUSION: The level of knowledge was satisfactory among healthcare providers with neutral level of attitude, practice, and familiarity regarding disaster preparedness. Follow-up research is necessary for maximizing ED preparedness.


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title: Antigen Sparing and Enhanced Protection Using A Novel rOv-ASP-1 Adjuvant in Aqueous Formulation with Influenza Vaccines

text: Influenza is one of the most common infectious diseases endangering the health of humans, especially young children and the elderly. Although vaccination is the most effective means of protection against influenza, frequent mutations in viral surface antigens, low protective efficacy of the influenza vaccine in the elderly, slow production process and the potential of vaccine supply shortage during a pandemic are significant limitations of current vaccines. Adjuvants have been used to enhance the efficacy of a variety of vaccines; however, no adjuvant is included in current influenza vaccines approved in the United States. In this study, we found that a novel adjuvant, rOv-ASP-1, co-administrated with inactivated influenza vaccine using an aqueous formulation, substantially improved the influenza-specific antibody response and protection against lethal infection in a mouse model. rOv-ASP-1 enhanced the magnitude of the specific antibody response after immunization with low doses of influenza vaccine, allowing antigen-sparring by 10-fold. The rOv-ASP-1 formulated vaccine induced a more rapid response and a stronger Th1-associated antibody response compared to vaccine alone and to the vaccine formulated with the adjuvant alum. Importantly, rOv-ASP-1 significantly enhanced cross-reactive antibody responses and protection against challenge with an antigenically distinct strain. These results demonstrate that rOv-ASP-1 is an effective adjuvant that: 1) accelerates and enhances the specific antibody response induced by influenza vaccine; 2) allows for antigen sparing; and 3) augments a Th1-biased and cross-reactive antibody response that confers protection against an antigenically distinct strain.


title: Prevalence and molecular characterization of porcine Picobirnavirus in piglets of North East Region of India

text: Picobirnaviruses (PBVs) have been recognized as one of the important causal viral agents of gastroenteritis in several animal species especially in young immunocompromised hosts. In this study, we report the prevalence and molecular epidemiology of porcine PBVs from North Eastern Hilly region of India. A total of 457 fecal samples from piglets were collected from local (n = 130) and cross (n = 327) breed piglets in different seasons for 2 years. All the samples were subjected to RNA-PAGE and RT-PCR analysis for detection of PBVs. A total of 4.59 and 11.15% samples were recorded as positive for PBVs by RNA-PAGE and RT-PCR, respectively. Rate of detection was higher from diarrhoeic animals (13.56%) compared to non-diarrhoeic (4.23%) animals. Higher prevalence rate was observed from unorganized farms (14.22%) compared to organized farms (8.0%) with slightly higher detection from cross breed (11.62%) compared to local breed (10.0%). Maximum cases of piglet diarrhea associated with PBVs were detected during summer (16.4%) and winter (14.39%) seasons compared to autumn (4.80%) and spring (6.45%). All the samples were positive for PBV genogroup I only. Based upon the sequence analysis, the isolates were unique and placed in separate clad and were not closely associated with any other Indian isolates of PBVs so far. Two isolates were closely related with one Chinese isolate recovered from sewage water. This is the first systematic study of prevalence of PBVs associated with piglet diarrhea.


title: COVID-19 transmission in Mainland China is associated with temperature and humidity: A time-series analysis

text: Abstract COVID-19 has become a pandemic. The influence of meteorological factors on the transmission and spread of COVID-19 is of interest. This study sought to examine the associations of daily average temperature (AT) and relative humidity (ARH) with the daily count of COVID-19 cases in 30 Chinese provinces (in Hubei from December 1, 2019 to February 11, 2020 and in other provinces from January 20, 2020 to Februarys 11, 2020). A Generalized Additive Model (GAM) was fitted to quantify the province-specific associations between meteorological variables and the daily cases of COVID-19 during the study periods. In the model, the 14-day exponential moving averages (EMAs) of AT and ARH, and their interaction were included with time trend and health-seeking behavior adjusted. Their spatial distributions were visualized. AT and ARH showed significantly negative associations with COVID-19 with a significant interaction between them (0.04, 95% confidence interval: 0.004–0.07) in Hubei. Every 1 °C increase in the AT led to a decrease in the daily confirmed cases by 36% to 57% when ARH was in the range from 67% to 85.5%. Every 1% increase in ARH led to a decrease in the daily confirmed cases by 11% to 22% when AT was in the range from 5.04 °C to 8.2 °C. However, these associations were not consistent throughout Mainland China.


title: Antiviral activity of dried extract of Stevia

text: The biological (antiviral) activity of a dried purified extract of Stevia was evaluated in vitro. Tests were performed using Teschen disease virus, infectious rhinotracheitis virus, and human coronavirus.


title: Chapter 22 Integrated Sensor Systems and Data Fusion for Homeland Protection

text: Abstract This chapter addresses the application of data and information fusion to the design of integrated systems in the Homeland Protection (HP) domain. HP is a wide and complex domain: systems in this domain are large (in terms of size and scope) integrated (each subsystem cannot be considered as an isolated system) and different in purpose. Such systems require a multidisciplinary approach for their design and analysis and they are necessarily required to provide data and information fusion in the most general sense. The first data fusion algorithms employed in real systems in the radar field go back to the early seventies; now a days new concepts have been developed and spread to be applied to very complex systems with the aim to achieve the highest level of intelligence as possible and hopefully to support decision. Data fusion is aimed to enhance situation awareness and decision making through the combination of information/data obtained by networks of homogeneous and/or heterogeneous sensors. The aim of this chapter is to give an overview of the several approaches that can be followed to design and analyze systems for homeland protection. Different fusion architectures can be drawn on the basis of the employed algorithms: they are analyzed under several aspects in this chapter. Real study cases applied to real world problems of homeland protection are provided in the chapter.


Recovery from SARS-CoV-2 infection is Associated with Serum BDNF Restoration


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title: Co-Infections in Children Hospitalised for Bronchiolitis: Role of Roomsharing

text: BACKGROUND: Bronchiolitis is a major cause for hospitalisation in young children during the winter season, with respiratory syncytial virus (RSV) as the main causative virus. Apart from standard hygiene measures, cohorting of RSV-infected patients separately from RSV-negative patients is frequently applied to prevent cross-infection, although evidence to support this practice is lacking. The objective is to evaluate the risk of room sharing between RSV-positive and RSV-negative patients. METHODS: We performed a prospective observational cohort study in children < 2 years hospitalised with acute bronchiolitis. During the first day of admission, patients shared one room, pending results of virological diagnosis (PCR). When diagnostic results were available, RSV-positive and RSV-negative patients were separated. Standard hygienic measures (gowns, gloves, masks, hand washing) were used in all patients. RESULTS: We included 48 patients (83% RSV-positive). Co-infection was found in nine patients at admission, and two during hospitalisation (23%). The two patients with acquired co-infection had been nursed in a single room during the entire admission. None of 37 patients sharing a room with other bronchiolitis patients (20 with patients with a different virus) were co-infected during admission. Disease severity in co-infection was not worse than in mono-infection. CONCLUSION: One in five patients with bronchiolitis was co-infected, but co-infection acquired during admission was rare and was not associated with more severe disease. Room sharing between RSV-positive and RSV-negative patients (on the first day of admission) did not influence the risk of co-infection, suggesting that cohorting of RSV-infected patients separate from non-RSV-infected patients may not be indicated.


title: Registered nurses are at increased risk of hospitalization for infectious diseases and perinatal complications: A population-based observational study

text: Abstract Background Nursing staff spend long periods in high-risk working environments. Objective The purpose of this study was to compare the hospitalization risk between nursing staff and the general population. Design This study adopted a retrospective observational design. Setting Data from the Taiwan National Health Insurance Research Database from 2011 to 2013 were analyzed. Method The standardized hospitalization ratio model was used to analyze the relative risk of hospitalization for various diseases between nursing staff and the general population. Results A total of 33,267 numbers of nursing staff in Taiwan were hospitalized, an overall crude hospitalization rate of 21.5%. After controlling for gender, calendar year, and age of nursing staff, the standardized hospitalization ratio of female nursing staff was significantly higher compared to the general population for infectious and parasitic diseases (SHR = 121.05, 95% CI = 112.66–129.89), diseases of the respiratory system (SHR = 105.12, 95% CI = 100.60–109.80), complications of pregnancy, childbirth, and the puerperium (SHR = 102.59, 95% CI = 100.85–104.35), and diseases of the skin and subcutaneous tissue (SHR = 109.71, 95% CI = 101.10–118.86). Conclusions Nursing staff have a significantly higher hospitalization risk compared to the general population for infectious and parasitic diseases, diseases of the respiratory system, complications of pregnancy, childbirth, and puerperium, and diseases of the skin and subcutaneous tissue. This may be associated with the job characteristics and environment of nursing staff.


title: The COVID-19 Pandemic: A Month of Bioethics in Finland—ADDENDUM

text: The role of bioethicists amidst crises like the COVID-19 pandemic is not well defined. As professionals in the field, they should respond, but how? The observation of the early days of pandemic confinement in Finland showed that moral philosophers with limited experience in bioethics tended to apply their favorite theories to public decisions with varying results. Medical ethicists were more likely to lend support to the public authorities by soothing or descriptive accounts of the solutions assumed. These are approaches that Tuija Takala has called the firefighting and window dressing models of bioethics. Human rights lawyers drew attention to the flaws of the government’s regulative thinking. Critical bioethicists offered analyses of the arguments presented and the moral and political theories that could be used as the basis of good and acceptable decisions.


Is a vitamin D fortification strategy needed?


title: The attenuation of vaccinia Tian Tan strain by the removal of the viral M1L-K2L genes

text: Abstract To generate a safe vaccinia Tian Tan (VTT)-based vaccine vector, it is necessary to develop a method to attenuate the virus. A modified VTT (MVTT2-GFP) was constructed by replacing the viral M1L-K2L genes with a GFP gene. In comparison to the parental VTT, MVTT2-GFP lost its replication capacity in rabbit RK13 and human HeLa cell lines. The life cycle of viral replication was blocked at different stages in these two cell lines as determined by electron microscope examination. MVTT2-GFP was less virulent than VTT for 100-fold by measuring mouse body weight loss after intranasal viral inoculation and for 340-fold by determining the intracranial LD50 value in mice. The foreign GFP gene was stable genetically after 10 rounds of passage in Vero cells. Importantly, MVTT2-GFP elicited both humoral and cell-mediated immune responses to the GFP gene in mice. With two intramuscular inoculations of 105 PFU virus, the anti-GFP antibody reciprocal endpoint titer reached over 700 as determined by an ELISA. The number of IFN-γ secreting T cells reached over 350SFU per million splenocytes against a CD8+ T cell-specific epitope of GFP. Collectively, the removal of the M1L-K2L genes is a useful method to generate an attenuated vaccinia Tian Tan vaccine vector.


title: Viral G-quadruplexes: New frontiers in virus pathogenesis and antiviral therapy

text: Viruses are the most abundant organisms on our planet, affecting all living beings: some of them are responsible for massive epidemics that concern health, national economies and the overall welfare of societies. Although advances in antiviral research have led to successful therapies against several human viruses, still some of them cannot be eradicated from the host and most of them do not have any treatment available. Consequently, innovative antiviral therapies are urgently needed. In the past few years, research on G-quadruplexes (G4s) in viruses has boomed, providing powerful evidence for the regulatory role of G4s in key viral steps. Comprehensive bioinformatics analyses have traced putative G4-forming sequences in the genome of almost all human viruses, showing that their distribution is statistically significant and their presence highly conserved. Since the genomes of viruses are remarkably variable, high conservation rates strongly suggest a crucial role of G4s in the viral replication cycle and evolution, emphasizing the possibility of targeting viral G4s as a new pharmacological approach in antiviral therapy. Recent studies have demonstrated the formation and function of G4s in pathogens responsible for serious diseases, such as HIV-1, Hepatitis B and C, Ebola viruses, to cite a few. In this chapter, we present the state of the art on the structural and functional characterization of viral G4s in RNA viruses, DNA viruses and retroviruses. We also present the G4 ligands that provide further details on the viral G4 role and which, showing promising antiviral activity, which could be exploited for the development of innovative antiviral agents.


title: Antiviral Type I and Type III Interferon Responses in the Central Nervous System

text: The central nervous system (CNS) harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB) from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs) are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i) preventing neuroinvasion and infection of CNS cells; ii) the identity of IFN-producing cells in the CNS; iii) the antiviral activity of ISGs; and iv) the activity of viral proteins of neurotropic viruses that target the IFN pathway.


title: Autophagic effects of Chaihu (dried roots of Bupleurum Chinense DC or Bupleurum scorzoneraefolium WILD)

text: Chaihu, prepared from the dried roots of Bupleurum Chinense DC (also known as bei Chaihu in Chinese) or Bupleurum scorzoneraefolium WILD (also known as nan Chaihu in Chinese), is a herbal medicine for harmonizing and soothing gan (liver) qi stagnation. Substantial pharmacological studies have been conducted on Chaihu and its active components (saikosaponins). One of the active components of Chaihu, saikosaponin-d, exhibited anticancer effects via autophagy induction. This article reviews the pharmacological findings for the roles of autophagy in the pharmacological actions of Chaihu and saikosaponins.


title: Perception and Performance of Preventive Behaviors for the Pandemic Influenza in Hospital Employees and Outpatients

text: PURPOSE: A new strain of the H1N1 subtype of influenza A virus resulted in a pandemic outbreak. In South Korea, cases of pandemic influenza have increased. Therefore, we explored perception or preventive behaviors for this virus in hospital employees and outpatients. MATERIALS AND METHODS: Data was collected from hospital employees and outpatients at three university hospitals located in Daegu, Gyeongju in South Korea between the 21st and 30th of September, 2009 using a self-administrated questionnaire. We estimated perception by components of The Health Belief Model (HBM), preventive behaviors consisted of avoidance behaviors, and the recommended behaviors by the Korea Center of Disease Control and Prevention (KCDC). Desire for vaccination was identified. RESULTS: The 1,837 participants comprised hospital employees (n = 880, 47.9%) and outpatients (n = 957, 52.1%). Of all hospital employees, 491 (55.8%) and 708 (80.5%) perceived susceptibility of the pandemic influenza and benefits of the preventive behaviors, respectively. Among all outpatients, 490 (51.2%) and 651 (68.0%) perceived susceptibility of the pandemic influenza and benefits of the preventive behaviors, respectively. Recommended preventative behaviors were adopted by 674 (76.6%) of hospital employees and 631 (65.9%) of outpatients. Vaccination was desired by 479 (54.4%) of hospital employees and 484 (50.6%) of outpatients. Factors influencing preventative behaviors included gender, economic status (for hospital employees) and educational level (for outpatients). All HBM components except perception of barriers were associated with the preventive behaviors in both groups. CONCLUSION: The majority of the surveyed hospital employees and outpatients perceived the benefits of preventive behaviors for pandemic influenza and performed them.


Functional Hemispherectomy in Adults: All We Have to Sphere Is Sphere Itself


docid: wupictvw

title: Plant-made vaccines and reagents for the One Health initiative

text: The One Health initiative is increasingly becoming a prominent discussion topic in animal and human health, with its focus on prevention of spread of zoonotic diseases, both in animals, and from animals to humans. An important part of One Health is that diagnostics and vaccines for diseases may be the same thing – and be used for both humans and animals. One potential problem standing in the way of wider adoption of One Health principles, though, is that use of conventional cell fermentation systems for production of the recombinant proteins that could be used as diagnostics or vaccines is often expensive and is not easily scalable. A solution to this may be the use of plants or plant cells as bioreactors: molecular farming, or the production of biologics in plants, is now a well-established science with many proofs of principle and important proofs of efficacy for especially animal vaccines. This review discusses how molecular farming could enable important advances in One Health, using as examples plant-made vacccines, reagents and therapeutics for influenza viruses, ebolaviruses, rabies virus, bunyaviruses and flaviviruses.


title: Electrochemical detection of viruses and antibodies: A mini review

text: [Figure: see text]


title: Human Mobility and COVID-19: A Negative Binomial Regression Analysis

text: Abstract Objectives This study aimed to examine the link between human mobility and the number of COVID-19 infected people in countries. Study Design Our dataset covers 144 countries for which complete data are available. In order to analyze the link between human mobility and COVID-19 infected people, our study focused on the volume of air travel, the number of airports and the Schengen system. Methods In order to analyze the variation in COVID-19 infected people in countries, we used negative binomial regression analysis. Results Our findings suggest a positive relationship between higher volume of airline passenger traffic carried in a country and higher numbers of COVID-19 patients. We further found that countries which have a higher number of airports are associated with higher number of COVID-19 cases. Schengen countries, countries which have higher population density and higher percentage of elderly population are also found to be more likely to have more COVID-19 cases than other countries. Conclusions The paper brings a novel insight into the COVID-19 pandemic from a human mobility perspective. Future research should assess the impacts of the scale of sea/bus/car travel on the epidemic. The findings of this paper are relevant for public health authorities, community and health-service providers and policy-makers.


title: A mechanical explanation of RNA pseudoknot function in programmed ribosomal frameshifting

text: The triplet-based genetic code requires that translating ribosomes maintain the reading frame of a messenger RNA faithfully to ensure correct protein synthesis(1). However, in programmed -1 ribosomal frameshifting(2), a specific subversion of frame maintenance takes place, wherein the ribosome is forced to shift one nucleotide backwards into an overlapping reading frame and to translate an entirely new sequence of amino acids. This process is indispensable in the replication of numerous viral pathogens, including HIV and the coronavirus associated with severe acute respiratory syndrome(3), and is also exploited in the expression of several cellular genes(4). Frameshifting is promoted by an mRNA signal composed of two essential elements: a heptanucleotide ‘slippery’ sequence(5) and an adjacent mRNA secondary structure, most often an mRNA pseudoknot(6). How these components operate together to manipulate the ribosome is unknown. Here we describe the observation of a ribosome–mRNA pseudoknot complex that is stalled in the process of -1 frameshifting. Cryoelectron microscopic imaging of purified mammalian 80S ribosomes from rabbit reticulocytes paused at a coronavirus pseudoknot reveals an intermediate of the frameshifting process. From this it can be seen how the pseudoknot interacts with the ribosome to block the mRNA entrance channel, compromising the translocation process and leading to a spring-like deformation of the P-site transfer RNA. In addition, we identify movements of the likely eukaryotic ribosomal helicase and confirm a direct interaction between the translocase eEF2 and the P-site tRNA. Together, the structural changes provide a mechanical explanation of how the pseudoknot manipulates the ribosome into a different reading frame. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature04735) contains supplementary material, which is available to authorized users.


title: Recombinant baculovirus expressing the FrC-OVA protein induces protective antitumor immunity in an EG7-OVA mouse model

text: BACKGROUND: The baculovirus (BV) Autographa californica multiple nuclear polyhedrosis virus has been used in numerous protein expression systems because of its ability to infect insect cells and serves as a useful vaccination vector with several benefits, such as its low clinical risks and posttranslational modification ability. We recently reported that dendritic cells (DCs) infected with BV stimulated antitumor immunity. The recombinant BV (rBV) also strongly stimulated peptide-specific T-cells and antitumor immunity. In this study, the stimulation of an immune response against EG7-OVA tumors in mice by a recombinant baculovirus-based combination vaccine expressing fragment C-ovalbumin (FrC-OVA-BV; rBV) was evaluated. RESULTS: We constructed an rBV expressing fragment C (FrC) of tetanus toxin containing a promiscuous MHC II-binding sequence and a p30-ovalbumin (OVA) peptide that functions in the MHC I pathway. The results showed that rBV activated the CD8(+) T-cell-mediated response much more efficiently than the wild-type BV (wtBV). Experiments with EG7-OVA tumor mouse models showed that rBV significantly decreased tumor volume and increased survival compared with those in the wild-type BV or FrC-OVA DNA vaccine groups. In addition, a significant antitumor effect of classic prophylactic or therapeutic vaccinations was observed for rBV against EG7-OVA-induced tumors compared with that in the controls. CONCLUSION: Our findings showed that FrC-OVA-BV (rBV) induced antitumor immunity, paving the way for its use in BV immunotherapy against malignancies.


title: AMP-Activated Kinase Restricts Rift Valley Fever Virus Infection by Inhibiting Fatty Acid Synthesis

text: The cell intrinsic innate immune responses provide a first line of defense against viral infection, and often function by targeting cellular pathways usurped by the virus during infection. In particular, many viruses manipulate cellular lipids to form complex structures required for viral replication, many of which are dependent on de novo fatty acid synthesis. We found that the energy regulator AMPK, which potently inhibits fatty acid synthesis, restricts infection of the Bunyavirus, Rift Valley Fever Virus (RVFV), an important re-emerging arthropod-borne human pathogen for which there are no effective vaccines or therapeutics. We show restriction of RVFV both by AMPK and its upstream activator LKB1, indicating an antiviral role for this signaling pathway. Furthermore, we found that AMPK is activated during RVFV infection, leading to the phosphorylation and inhibition of acetyl-CoA carboxylase, the first rate-limiting enzyme in fatty acid synthesis. Activating AMPK pharmacologically both restricted infection and reduced lipid levels. This restriction could be bypassed by treatment with the fatty acid palmitate, demonstrating that AMPK restricts RVFV infection through its inhibition of fatty acid biosynthesis. Lastly, we found that this pathway plays a broad role in antiviral defense since additional viruses from disparate families were also restricted by AMPK and LKB1. Therefore, AMPK is an important component of the cell intrinsic immune response that restricts infection through a novel mechanism involving the inhibition of fatty acid metabolism.


title: An enteric coronavirus of the rabbit: Detection by immunoelectron microscopy and identification of structural polypeptides

text: The immunoelectron microscopy (IEM) technique has been used for the detection of a rabbit enteric coronavirus (RECV). Immune serum was prepared in guinea pigs; the viral antigen used for the immunization procedure was obtained from the caecum of a sick rabbit, concentrated by centrifugation and purified on Percoll gradient. In order to identify the viral particles used in the immunization procedure, the protein pattern of the particles was determined by electrophoresis and compared with the pattern of other known coronaviruses. Analysis of structural polypeptides of the purified viral particles revealed a pattern similar to that reported for other coronaviruses. These polypeptides cross reacted with two other coronavirus specific immune sera (IBV and TGE). IEM assay of fecal samples collected from healthy and sick rabbits showed the presence of immune aggregates in specimens from both sick and healthy rabbits. Those aggregates contained viral particules sharing morphological characteristics with other coronaviruses. Furthermore, IEM assay was shown to be more sensitive than a direct EM procedure to detect coronavirus particles in rabbit feces. This assay also allowed the detection of a larger number of chronic carriers.


title: Use of a Small Peptide Fragment as an Inhibitor of Insulin Fibrillation Process: A Study by High and Low Resolution Spectroscopy

text: A non-toxic, nine residue peptide, NIVNVSLVK is shown to interfere with insulin fibrillation by various biophysical methods. Insulin undergoes conformational changes under certain stress conditions leading to amyloid fibrils. Fibrillation of insulin poses a problem in its long-term storage, reducing its efficacy in treating type II diabetes. The dissociation of insulin oligomer to monomer is the key step for the onset of fibrillation. The time course of insulin fibrillation at 62°C using Thioflavin T fluorescence shows an increase in the lag time from 120 min without peptide to 236 min with peptide. Transmission electron micrographs show branched insulin fibrils in its absence and less inter-fibril association in its presence. Upon incubation at 62°C and pH 2.6, insulin lost some α-helical structure as seen by Fourier transformed infra-red spectroscopy (FT-IR), but if the peptide is added, secondary structure is almost fully maintained for 3 h, though lost partially at 4 h. FT-IR spectroscopy also shows that insulin forms the cross beta structure indicative of fibrils beyond 2 h, but in the presence of the peptide, α-helix retention is seen till 4 h. Both size exclusion chromatography and dynamic light scattering show that insulin primarily exists as trimer, whose conversion to a monomer is resisted by the peptide. Saturation transfer difference nuclear magnetic resonance confirms that the hydrophobic residues in the peptide are in close contact with an insulin hydrophobic groove. Molecular dynamics simulations in conjunction with principal component analyses reveal how the peptide interrupts insulin fibrillation. In vitro hemolytic activity of the peptide showed insignificant cytotoxicity against HT1080 cells. The insulin aggregation is probed due to the inter play of two key residues, Phe(B24) and Tyr(B26) monitored from molecular dynamics simulations studies. Further new peptide based leads may be developed from this nine residue peptide.


title: A Habitat-Based Model for the Spread of Hantavirus Between Reservoir and Spillover Species

text: New habitat-based models for spread of hantavirus are developed which account for interspecies interaction. Existing habitat-based models do not consider interspecies pathogen transmission, a primary route for emergence of new infectious diseases and reservoirs in wildlife and man. The modeling of interspecies transmission has the potential to provide more accurate predictions of disease persistence and emergence dynamics. The new models are motivated by our recent work on hantavirus in rodent communities in Paraguay. Our Paraguayan data illustrate the spatial and temporal overlap among rodent species, one of which is the reservoir species for Jabora virus and others which are spillover species. Disease transmission occurs when their habitats overlap. Two mathematical models, a system of ordinary differential equations (ODE) and a continuous-time Markov chain (CTMC) model, are developed for spread of hantavirus between a reservoir and a spillover species. Analysis of a special case of the ODE model provides an explicit expression for the basic reproduction number, ℛ(0), such that if ℛ(0) < 1, then the pathogen does not persist in either population but if ℛ(0) > 1, pathogen outbreaks or persistence may occur. Numerical simulations of the CTMC model display sporadic disease incidence, a new behavior of our habitat-based model, not present in other models, but which is a prominent feature of the seroprevalence data from Paraguay. Environmental changes that result in greater habitat overlap result in more encounters among various species that may lead to pathogen outbreaks and pathogen establishment in a new host.


docid: dzhoftzi

title: Granulocyte‐colony stimulating factor in COVID‐19: Is it stimulating more than just the bone marrow?


The pathogenic role of virus-specific antibody secreting cells in the CNS of rats resistant and susceptible to coronavirus-induced encephalitis


title: Deoxygenation of 5-O-benzoyl-1,2-isopropylidene-3-O-imidazolylthiocarbonyl-α-d-xylofuranose using dimethyl phosphite: an efficient alternate method towards a 3′-deoxynucleoside glycosyl donor

text: An efficient radical deoxygenation reaction of thiocarbonylimidazolyl activated glycoside analogue using dimethyl phosphite as hydrogen source and radical chain carrier was performed as a key step in a multi step synthesis towards a common 3-deoxy glycosyl donor for 3′-deoxynucleosides. This method has safety and cost advantages compared to the generally used radical reduction reagents.


title: Temporal Variations in the Distribution of West Nile Virus Within the United States; 2000–2008

text: West Nile Virus (WNV) is a serious illness that has affected thousands of people in the United States. Over 1,000 disease related deaths have occurred since its introduction to American soil in 1999. Spatial statistics are used to analyze distributional trends of human WNV cases from 2000 to 2008 through four analyses: Weighted Mean Center, Standard Deviational Ellipses, Global Moran’s I, and Getis-Ord-Gi* statistic (hot spot analysis). We conclude that the directional trend in cases has been from East to West with the area affected increasing with time. Hot spot analysis reveals that recurring counties with a high number of human cases have been in the metro areas of large cities. However, normalized results indicate that the rate of humans showing symptoms of WNV is greatest in rural areas, particularly the Great Plains. These results provide a foundation for future research in analyzing the most persistent hot spots in more detail. Furthermore, these findings may aid decision makers in identifying areas to target for mitigation strategies such as spraying, larval control, and public awareness.


docid: aztqzktw

title: Longitudinal Profiling of the Vaccination Coverage in Brazil Reveals a Recent Change in the Patterns Hallmarked by Differential Reduction Across Regions

text: Abstract Objective Vaccination coverage is decreasing worldwide, favoring potential reemergence of vaccine-preventable disease. Here, we performed a longitudinal characterization of the vaccination coverage in Brazil and compared the profiles between the distinct regions in the country to test whether there has been a substantial change over the last five years. Methods We retrieved de-identified data publicly available from the repository of the Brazilian Ministry of Health, comprising detailed information on vaccination coverage, in all age groups, between 1994 and 2019. We examined the vaccination coverage from the whole country and each Brazilian region, by year, and performed a time-series pattern analysis. Results A significant decrease in overall vaccination coverage across the country regions was observed between 2017 and 2019, especially in childhood immunization. BCG, Hepatitis B, influenza and rotavirus vaccines displayed a reduction in coverage. Conversely, vaccines against measles, mumps, rubella, varicella, and meningococcus had an increase in coverage. Region-specific changes in vaccination patterns within the study period were observed. Conclusions Substantial reduction in vaccination coverage was detected in Brazil, a country already highly susceptible to emergency of epidemic infectious diseases. Recursively evaluation of the immunization program actions may help to improve vaccination coverage and prevent new epidemics.


title: Chapter 8 Infectious Complications of Transfusion of Blood Components

text: Abstract Transfusions are lifesaving but are not without some risks. During the middle of the last century, infectious complications were common from transfusions. By the mid 1980s the risk of transfusion transmission of infections became much lower. With the advent of emerging diseases, however, infectious risks became more prominent for a period of time. Now we live in a time where death from transfusion transmission is 10%–15% of all transfusion-associated deaths and is the lowest in history. As the risks are identified and new screens or processes are put in place, the associated transfusion transmission of infection will continue to have reducing risks and blood supply will continue to be safer still.


title: Calming the Cytokine Storm in Pneumonia by Biomimetic Nanoparticles

text: Recently, the Wang group at Soochow University and the Gu group at the University of California, Los Angeles demonstrated the targeting ability of platelet-derived extracellular vesicles to deliver anti-inflammatory drug [5-(p-fluorophenyl)-2-ureido] thiophene-3-carboxamide (TPCA-1) to pneumonia for calming the local cytokine storm in acute lung injury.


title: Common RNA replication signals exist among group 2 coronaviruses: evidence for in vivo recombination between animal and human coronavius molecules

text: Abstract 5′ and 3′ UTR sequences on the coronavirus genome are known to carry cis-acting elements for DI RNA replication and presumably also virus genome replication. 5′ UTR-adjacent coding sequences are also thought to harbor cis-acting elements. Here we have determined the 5′ UTR and adjacent 289-nt sequences, and 3′ UTR sequences, for six group 2 coronaviruses and have compared them to each other and to three previously reported group 2 members. Extensive regions of highly similar UTR sequences were found but small regions of divergence were also found indicating group 2 coronaviruses could be subdivided into those that are bovine coronavirus (BCoV)-like (BCoV, human respiratory coronavirus-OC43, human enteric coronavirus, porcine hemagglutinating encephalomyelitis virus, and equine coronavirus) and those that are murine hepatitis virus (MHV)-like (A59, 2, and JHM strains of MHV, puffinosis virus, and rat sialodacryoadenitis virus). The 3′ UTRs of BCoV and MHV have been previously shown to be interchangeable. Here, a reporter-containing BCoV DI RNA was shown to be replicated by all five BCoV-like helper viruses and by MHV-H2 (a human cell-adapted MHV strain), a representative of the MHV-like subgroup, demonstrating group 2 common 5′ and 3′ replication signaling elements. BCoV DI RNA, furthermore, acquired the leader of HCoV-OC43 by leader switching, demonstrating for the first time in vivo recombination between animal and human coronavirus molecules. These results indicate that common replication signaling elements exist among group 2 coronaviruses despite a two-cluster pattern within the group and imply there could exist a high potential for recombination among group members.


title: CCR5 Signaling Suppresses Inflammation and Reduces Adverse Remodeling of the Infarcted Heart, Mediating Recruitment of Regulatory T Cells

text: Myocardial infarction triggers an inflammatory reaction that is involved in cardiac remodeling. Cardiac repair is dependent on regulatory mechanisms that suppress inflammation and prevent excessive matrix degradation. Chemokine induction in the infarcted heart mediates recruitment of leukocyte subsets with distinct properties. We demonstrate that signaling through the CC chemokine receptor 5 (CCR5) prevents uncontrolled postinfarction inflammation and protects from adverse remodeling by recruiting suppressive mononuclear cells. CCR5 and its ligands macrophage inflammatory protein (MIP)−1α and MIP-1β were markedly induced in the infarcted mouse myocardium. In addition, almost 40% of the mononuclear cells infiltrating the infarct expressed CCR5. CCR5(−/−) mice exhibited marked upregulation of proinflammatory cytokine and chemokine expression in the infarct. In wild-type infarcts CCR5(+) mononuclear cells had anti-inflammatory properties, expressing higher levels of IL-10 than CCR5(−) cells. In contrast, mononuclear cells isolated from CCR5(−/−) infarcts had reduced IL-10 expression. Moreover, enhanced inflammation in the absence of CCR5 was associated with impaired recruitment of CD4(+)/foxp3(+) regulatory T cells (Tregs). The CCR5(+) Treg subset exhibited increased IL-10 expression, reflecting potent anti-inflammatory activity. Accentuated inflammation in CCR5(−/−) infarcts was associated with increased matrix metalloproteinase (MMP) expression, reduced TIMP levels, and enhanced MMP-2 and MMP-9 activity, resulting in worse cardiac dilation. These results suggest that CCR5-mediated Treg recruitment may restrain postinfarction inflammation, preventing excessive matrix degradation and attenuating adverse remodeling.


title: Depression, Anxiety, Stress Levels of Physicians and Associated Factors In Covid-19 Pandemics

text: AIM: To investigate anxiety, stress, and depression levels of physicians during the Covid-19 outbreak and explored associated factors in both clinical and general site. METHODS: An online survey is conducted to asses psychological responses of healthcare workers and related factors during Covid-19 outbreak. It is consisted of three subsections covering the following areas: 1) sociodemographic data 2) information on individuals` working condition 3) Depression Anxiety and Stress Scale-21 (DAS-21). RESULTS: Of all 442 participants, 286 (64.7%) had symptoms of depression, 224 (51.6%) anxiety, and 182 (41.2%) stress. Being female, young, and single, having less work experience, working in frontline were associated with higher scores, whereas having a child was associated with lower scores in each subscale. Factors found to be associated with higher DAS-21 total scores in frontline workers were as follows: increased weekly working hours, increased number of Covid-19 patients cared for, lower level of support from peers and supervisors, lower logistic support, and lower feelings of competence during Covid-19 related tasks. CONCLUSIONS: Our findings highlight the factors which need to be taken into consideration to protect the mental wellbeing of doctors while fighting with a disaster that has major impacts on society worldwide.


Interactions Between Sars Coronavirus and its Receptor


title: Smart textiles for infection control management

text: Infection, cross-infection, and infectious diseases are critical for health care personnel and patients in hospitals mainly owing to multi-drug-resistance pathogens. Textile materials and garments used in hospitals promote cross-infection as they are used as a vehicle by the pathogenic disease-causing bacteria to spread the infection. However, smart textile materials play a vital role in protecting against the transmission of diseases not only in hospitals but also in other environments where people gather in large numbers. This chapter discusses the application of such materials for infection control management including wound infection management in hospitals. The role of hospital protective garments is summarised. Test methods and standards that cover surgical gowns, drapes, and clean air suits are highlighted.


Spine Fellowship Training Reorganizing during a Pandemic: Perspectives from a Tertiary Orthopaedic Specialty Center in the Epicenter of Outbreak


title: A Plasma Biomarker Panel of Four MicroRNAs for the Diagnosis of Prostate Cancer

text: Prostate cancer is diagnosed in over 1 million men every year globally, yet current diagnostic modalities are inadequate for identification of significant cancer and more reliable early diagnostic biomarkers are necessary for improved clinical management of prostate cancer patients. MicroRNAs (miRNAs) modulate important cellular processes/pathways contributing to cancer and are stably present in body fluids. In this study we profiled 372 cancer-associated miRNAs in plasma collected before (~60% patients) and after/during commencement of treatment (~40% patients), from age-matched prostate cancer patients and healthy controls, and observed elevated levels of 4 miRNAs - miR-4289, miR-326, miR-152-3p and miR-98-5p, which were validated in an independent cohort. The miRNA panel was able to differentiate between prostate cancer patients and controls (AUC = 0.88). Analysis of published miRNA transcriptomic data from clinical samples demonstrated low expression of miR-152-3p in tumour compared to adjacent non-malignant tissues. Overexpression of miR-152-3p increased proliferation and migration of prostate cancer cells, suggesting a role for this miRNA in prostate cancer pathogenesis, a concept that was supported by pathway analysis of predicted miR-152-3p target genes. In summary, a four miRNA panel, including miR-152-3p which likely targets genes with key roles in prostate cancer pathogenesis, has the potential to improve early prostate cancer diagnosis.


title: Antigenic and biological diversity of feline coronaviruses: feline infectious peritonitis and feline enteritis virus

text: Antigenically related feline coronaviruses cause two distinct disease manifestations in infected cats. The diseases are feline infectious peritonitis (FIP), in which the virus is widely disseminated, and feline enteric coronavirus (FECV), a mild disease in which the virus is usually limited to the villi. These two viruses were found to differ in their growth in cell culture. FIPV grows to higher titer, forms larger plaques and switches off host cell protein synthesis more effectively than FECV. Cross neutralization studies showed antigenic differences between the strains. There also appeared to be a difference in the nucleoprotein molecular weight of the viruses causing these two different disease syndromes.


SARS: health care work can be hazardous to health


title: Chapter 18 Family Arteriviridae

text: Abstract The family Arteriviridae is one of four families in the order Nidovirales. Arteriviruses are enveloped, plus-strand RNA viruses with genomes of 12.7–15.7kb. The overall genome organization and gene expression strategy of the arteriviruses is highly similar to the coronaviruses. Notably they use a discontinuous transcription strategy for synthesis of subgenomic mRNAs. There are no recognized human pathogens among the arteriviruses. Members of the family include equine arteritis virus and porcine reproductive and respiratory syndrome virus, the latter an economically important pathogen of pigs.


title: Fulminant Acute Kidney Injury in a Young Patient with Novel Coronavirus 2019

text: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting more than 200 countries and 180,000 cases in the United States. While the outbreak began in China, the number of cases outside of China exceeded those in China on March 15, 2020 and are currently rising at an exponential rate. The number of fatalities in the United States are expected to exceed more than Italy and China. The disease is characterized predominantly as an acute respiratory illness. However, preliminary data suggests that kidney is a target for the virus and deterioration of renal function was associated with poor outcomes including in-hospital mortality. We present a report of a patient with COVID-19 who presented with acute onset of symptoms and normal renal function at baseline but rapidly deteriorated resulting in death. The timing of decline in renal function correlated with his worsening clinical status. He was started on continuous veno-venous hemofiltration without signs of clinical benefit. We also present the possible mechanisms for acute kidney injury in these patients. We performed a review of the emerging literature by searching PubMed, Google Scholar, and EMBASE for studies and/or case series published on this topic. Acute kidney injury might help risk stratify critically ill patients on a fatal course of COVID-19.


title: Smoking Is Associated With COVID-19 Progression: A Meta-analysis

text: INTRODUCTION: Smoking depresses pulmonary immune function and is a risk factor contracting other infectious diseases and more serious outcomes among people who become infected. This paper presents a meta-analysis of the association between smoking and progression of the infectious disease COVID-19. METHODS: PubMed was searched on April 28, 2020, with search terms “smoking”, “smoker*”, “characteristics”, “risk factors”, “outcomes”, and “COVID-19”, “COVID”, “coronavirus”, “sar cov-2”, “sar cov 2”. Studies reporting smoking behavior of COVID-19 patients and progression of disease were selected for the final analysis. The study outcome was progression of COVID-19 among people who already had the disease. A random effects meta-analysis was applied. RESULTS: We identified 19 peer-reviewed papers with a total of 11,590 COVID-19 patients, 2,133 (18.4%) with severe disease and 731 (6.3%) with a history of smoking. A total of 218 patients with a history of smoking (29.8%) experienced disease progression, compared with 17.6% of non-smoking patients. The meta-analysis showed a significant association between smoking and progression of COVID-19 (OR 1.91, 95% confidence interval [CI] 1.42-2.59, p = 0.001). Limitations in the 19 papers suggest that the actual risk of smoking may be higher. CONCLUSIONS: Smoking is a risk factor for progression of COVID-19, with smokers having higher odds of COVID-19 progression than never smokers. IMPLICATIONS: Physicians and public health professionals should collect data on smoking as part of clinical management and add smoking cessation to the list of practices to blunt the COVID-19 pandemic.


title: Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach

text: Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driven selective pressure. Results showed an excess of variants correlated with virus diversity in genes involved in immune response and in the biosynthesis of glycan structures functioning as viral receptors; a significantly higher than expected number of variants was also seen in genes encoding proteins that directly interact with viral components. Genome-wide analyses identified 441 variants significantly associated with virus-diversity; these are more frequently located within gene regions than expected, and they map to 139 human genes. Analysis of functional relationships among genes subjected to virus-driven selective pressure identified a complex network enriched in viral products-interacting proteins. The novel approach to the study of infectious disease epidemiology presented herein may represent an alternative to classic genome-wide association studies and provides a large set of candidate susceptibility variants for viral infections.


title: Etiology of community acquired pneumonia among children in India: prospective, cohort study

text: BACKGROUND: Childhood community acquired pneumonia (CAP) is a significant problem in developing countries, and confirmation of microbial etiology is important for individual, as well as public health. However, there is paucity of data from a large cohort, examining multiple biological specimens for diverse pathogens (bacteria and viruses). The Community Acquired Pneumonia Etiology Study (CAPES) was designed to address this knowledge gap. METHODS: We enrolled children with CAP (based on WHO IMCI criteria of tachypnea with cough or breathing difficulty) over 24 consecutive months, and recorded presenting symptoms, risk factors, clinical signs, and chest radiography. We performed blood and nasopharyngeal aspirate (NPA) bacterial cultures, and serology (Mycoplasma pneumoniae, Chlamydophila pneumoniae). We also performed multiplex PCR for 25 bacterial/viral species in a subgroup representing 20% of the cohort. Children requiring endotracheal intubation underwent culture and PCR of bronchoalveolar lavage (BAL) specimens. FINDINGS: We enrolled 2345 children. NPA and blood cultures yielded bacteria in only 322 (13.7%) and 49 (2.1%) children respectively. In NPA, Streptococcus pneumoniae (79.1%) predominated, followed by Haemophilus influenzae (9.6%) and Staphylococcus aureus (6.8%). In blood, S. aureus (30.6%) dominated, followed by S. pneumoniae (20.4%) and Klebsiella pneumoniae (12.2%). M. pneumoniae and C. pneumoniae serology were positive in 4.3% and 1.1% respectively. Multiplex PCR in 428 NPA specimens identified organisms in 422 (98.6%); of these 352 (82.2%) had multiple organisms and only 70 (16.4%) had a single organism viz. S. pneumoniae: 35 (50%), Cytomegalovirus (CMV): 13 (18.6%), Respiratory Syncytial Virus (RSV): 9 (12.9%), other viruses: 6 (8.7%), S. aureus: 5 (7.1%), and H. influenzae: 2 (2.9%). BAL PCR (n = 30) identified single pathogens in 10 (S. pneumoniae–3, CMV–3, S. aureus–2, H. influenzae–2) and multiple pathogens in 18 children. There were 108 (4.6%) deaths. The pattern of pathogens identified did not correlate with pneumonia severity or mortality. CONCLUSIONS: The majority of children with CAP have multiple pathogens (bacteria and viruses). S. pneumoniae and S. aureus predominate in NPA and blood respectively. CMV and RSV were the dominant respiratory viruses in NPA and BAL. The presence of multiple pathogens, especially organisms associated with nasopharyngeal carriage, precludes confirmation of a causal relationship in most cases.


title: Proposed guidelines for screening of hyperglycemia in patients hospitalized with COVID-19 in low resource settings

text: BACKGROUND AND AIMS: The coronavirus disease 2019 (COVID-19) pandemic has immensely strained the healthcare system worldwide. Diabetes has emerged as a major comorbidity in a large proportion of patients infected with COVID-19 and is associated with poor health outcomes. We aim to provide a practical guidance on screening of hyperglycemia in persons without known diabetes in low resource settings. METHODS: We reviewed the available guidelines on this subject and proposed an algorithm based on simple measures of blood glucose (BG) which can be implemented by healthcare workers with lesser expertise in low resource settings. RESULTS: We propose that every hospitalized patient with COVID-19 infection undergo a paired capillary BG assessment (pre-meal and 2-h post-meal). Patients with pre-meal BG < 7.8 mmol/L (140 mg/dL) and post-meal BG < 10.0 mmol/L (180 mg/dL) may not merit further monitoring. On the other hand, those with one or more value above these thresholds should undergo capillary BG monitoring (pre-meals and 2 h after dinner) for the next 24 h. When two or more (≥50%) such values are significantly elevated [pre-meal ≥8.3 mmol/L (150 mg/dL) and post-meal ≥11.1 mmol/L (200 mg/dL)], pharmacotherapy should be immediately initiated. On the other hand, in patients with modest elevation of one or more values [pre-meal 7.8–8.3 mmol/L (140–150 mg/dL) and post-meal 10.0–11.1 mmol/L (180–200 mg/dL)], dietary modifications should be initiated and pharmacotherapy considered only if BG control remains suboptimal. CONCLUSION: We highlight strategies for screening of hyperglycemia in persons without known diabetes treated for COVID-19 infection in low resource settings. This guidance may well be applied to other settings in the near future.


title: Epidemiology of Respiratory Pathogens among Elderly Nursing Home Residents with Acute Respiratory Infections in Corsica, France, 2013–2017

text: BACKGROUND: The current study aims to describe the demographical and clinical characteristics of elderly nursing home (NH) residents with acute respiratory infections (ARIs) during four winter seasons (2013/2014–2016/2017), as well as the microbiological etiology of these infections. METHODS: Seventeen NHs with at least one ARI resident in Corsica, France, were included. An ARI resident was defined as a resident developing a sudden onset of any constitutional symptoms in addition to any respiratory signs. Nasopharyngeal swabs from ARI residents were screened for the presence of 21 respiratory agents, including seasonal influenza viruses. RESULTS: Of the 107 ARI residents enrolled from NHs, 61 (57%) were positive for at least one of the 21 respiratory pathogens. Forty-one (38.3%) of the 107 ARI residents had influenza: 38 (92%) were positive for influenza A (100% A(H3N2)) and three (8%) for influenza B/Victoria. Axillary fever (≥38°C) was significantly more common among patients infected with influenza A(H3N2). CONCLUSION: The circulation of seasonal respiratory viruses other than influenza A(H3N2) seems to be sporadic among elderly NH residents. Investigating the circulation of respiratory viruses in nonwinter seasons seems to be important in order to understand better the dynamic of their year-round circulation in NHs.


title: Cytosolic DNA‐sensing immune response and viral infection

text: How host cells recognize many kinds of RNA and DNA viruses and initiate innate antiviral responses against them has not yet been fully elucidated. Over the past decade, investigations into the mechanisms underlying these antiviral responses have focused extensively on immune surveillance sensors that recognize virus‐derived components (such as lipids, sugars and nucleic acids). The findings of these studies have suggested that antiviral responses are mediated by cytosolic or intracellular compartment sensors and their adaptor molecules (e.g., TLR, myeloid differentiation primary response 88, retinoic acid inducible gene‐I, IFN‐β promoter stimulator‐1, cyclic GMP‐AMP synthase and stimulator of IFN genes axis) for the primary sensing of virus‐derived nucleic acids, leading to production of type I IFNs, pro‐inflammatory cytokines and chemokines by the host cells. Thus, host cells have evolved an elaborate host defense machinery to recognize and eliminate virus infections. In turn, to achieve sustained viral infection and induce pathogenesis, viruses have also evolved several counteracting strategies for achieving immune escape by targeting immune sensors, adaptor molecules, intracellular kinases and transcription factors. In this review, we discuss recent discoveries concerning the role of the cytosolic nucleic acid‐sensing immune response in viral recognition and control of viral infection. In addition, we consider the regulatory machinery of the cytosolic nucleic acid‐sensing immune response because these immune surveillance systems must be tightly regulated to prevent aberrant immune responses to self and non‐self‐nucleic acids.


title: A Novel Construction of Genome Space with Biological Geometry

text: A genome space is a moduli space of genomes. In this space, each point corresponds to a genome. The natural distance between two points in the genome space reflects the biological distance between these two genomes. Currently, there is no method to represent genomes by a point in a space without losing biological information. Here, we propose a new graphical representation for DNA sequences. The breakthrough of the subject is that we can construct the moment vectors from DNA sequences using this new graphical method and prove that the correspondence between moment vectors and DNA sequences is one-to-one. Using these moment vectors, we have constructed a novel genome space as a subspace in R(N). It allows us to show that the SARS-CoV is most closely related to a coronavirus from the palm civet not from a bird as initially suspected, and the newly discovered human coronavirus HCoV-HKU1 is more closely related to SARS than to any other known member of group 2 coronavirus. Furthermore, we reconstructed the phylogenetic tree for 34 lentiviruses (including human immunodeficiency virus) based on their whole genome sequences. Our genome space will provide a new powerful tool for analyzing the classification of genomes and their phylogenetic relationships.


title: Clinical characteristics of patients with laboratory-confirmed influenza A(H1N1)pdm09 during the 2013/2014 and 2015/2016 clade 6B/6B.1/6B.2-predominant outbreaks

text: A novel pandemic influenza A(H1N1)pdm09 virus emerged in 2009 globally, and it continues to circulate in humans. The National Influenza Surveillance Network in Taiwan identified five A(H1N1)pdm09-predominant seasons, representing the 2009/2010, 2010/2011, 2012/2013, 2013/2014, and 2015/2016 outbreaks from 2009 to 2016. Independently, a retrospective cohort study (which enrolled 639 infected patients during the five seasons) was conducted at Chang Gung Memorial Hospital to explore the risk factors associated with influenza A(H1N1)pdm09-related complications. A phylogenetic analysis of hemagglutinin (HA) sequences showed that the circulating A(H1N1)pdm09 virus belonged to clades 1, 2, and 8 in 2009/2010; clades 3, 4, 5, and 7 in 2010/2011; clades 7 and 6C in 2012/2013; clades 6B in 2013/2014; and 6B/6B.1/6B.2 in 2015/2016. Compared to individuals infected in non-6B/6B.1/6B.2 seasons (2009/2010, 2010/2011, and 2012/2013), those infected in 6B/6B.1/6B.2 seasons (2013/2014 and 2015/2016) were at higher risk for influenza-related complications (adjusted odds ratio [aOR]: 1.6, 95% confidence interval [CI]: 1.0–2.8), pneumonia (aOR: 1.78, 95% CI: 1.04–3.04), mechanical ventilation (aOR: 2.6, 95% CI: 1.2–5.6), and acute respiratory distress syndrome (aOR: 5.5, 95% CI: 1.9–15.9). For the increased severity of infection during the influenza A(H1N1)pdm09 clade 6B/6B.1/6B.2 seasons, aspects related to the antigenic change of A(H1N1)pdm09 virus, immune response of the host, and environmental factors required further investigation.


title: Digestion pattern of reovirus outer capsid protein σ3 determined by mass spectrometry

text: Abstract Reovirus is an enteric virus comprising eight structural proteins that form a double-layered capsid. During reovirus entry into cells, the outermost capsid layer (composed of proteins σ3 and μ1C) is proteolytically processed to generate an infectious subviral particle (ISVP) that is subsequently uncoated to produce the transcriptionally active core particle. Kinetic studies suggest that protein σ3 is rapidly removed from virus particles and then protein μ1C is cleaved. Initial cleavage of μ1C has been well described and generates an amino (N)-terminal δ peptide and a carboxyl (C)-terminal φ peptide. However, cleavage and removal of σ3 is an extremely rapid event that has not been well defined. We have treated purified reovirus serotype 1 Lang virions with a variety of endoproteases. Time-course digestions with chymotrypsin, Glu-C, pepsin, and trypsin resulted in the initial generation of two peptides that were resolved in SDS–PAGE and analyzed by in-gel tryptic digestion and MALDI-Qq-TOFMS. Most tested proteases cut σ3 within a “hypersensitive” region between amino acids 217 and 238. In addition, to gain a better understanding of the sequence of subsequent proteolytic events that result in generation of reovirus subviral particles, time-course digestions of purified particles were performed under physiologic salt conditions and released peptide fragments ranging from 500 to 5000 Da were directly analyzed by MALDI-Qq-TOFMS. Trypsin digestion initially released a peptide that corresponded to the C-terminus of μ1C, followed by a peptide that corresponded to amino acids 214–236 of the σ3 protein. Other regions of μ1C were not observed until protein σ3 was completely digested. Similar experiments with Glu-C indicated the hypersensitive region of σ3 was cut first when virions were treated at pH values of 4.5 or 7.4, but treatment of virions with pepsin at pH 3.0 released different σ3 peptides, suggesting acid-induced conformational changes in this outer capsid protein. These studies also revealed that the N-terminus of σ3 is acetylated.


title: Wheezing exacerbations in early childhood: evaluation, treatment, and recent advances relevant to the genesis of asthma

text: Children who begin wheezing during early childhood are seen frequently by health care providers in primary care, in hospitals and emergency departments, and by allergists and pulmonologists. When young children, like the 2 year-old case presented here, are evaluated for wheezing, a frequent challenge for clinicians is to determine whether the symptoms represent transient, viral-induced wheezing, or whether sufficient risk factors are present to suspect that the child may experience recurrent wheezing and develop asthma. Most factors influencing prognosis are not mutually exclusive, are interrelated (i.e., cofactors), and often represent gene-environment interactions. Many of these risk factors have been, and continue to be, investigated in prospective studies in order to decipher their relative importance with the goal of developing new therapies and interventions in the future. The etiologies of wheezing in young children, diagnostic methods, treatment, prognostic factors, and potential targets for prevention of the development of asthma are discussed.


title: Retrograde Instrumentation of Surgically Resected Roots Using Controlled Memory Files: A Human Cadaver Study

text: INTRODUCTION: The purpose of this study is to evaluate the amount of residual obturation material of retroinstrumented surgically resected roots using controlled memory (CM) files and to evaluate the incidence of adverse treatment outcomes. METHODS: Thirty maxillary anterior teeth in human cadavers were selected and non-surgical root canal treatment was performed on these teeth. A standardized 4-mm osteotomy and a 3-mm root resection with as close to a zero-degree bevel as possible was made on each tooth. A microsurgical diamond tip was used to create a 1-2 mm starting point for each retropreparation. A 25/06 and 30/06 VTaper 2H (SS White, Lakewood, NJ) were bent at a about 90-degree angle to mimic the clinical and anatomical restrictions and used to create a retropreparation to a depth of 14-mm. Micro-CT scans were taken and analyzed for volume and percentage of residual obturation material at 5- and 10-mm. Additionally, the incidence of instrument separation and crack and ledge formation in the teeth were recorded. RESULTS: The median volume of residual obturation at 5- and 10-mm was 0.18 mm(3) (interquartile range of 0.36 mm(3)), and 1.97 mm(3) (interquartile range of 1.99 mm(3)) respectively. The overall incidence of file separation during retropreparation was 13.33% (4/30). Among the cases analyzed with micro-CT, none showed crack or ledge formation. CONCLUSIONS: Retroinstrumentation of surgically resected roots using controlled memory files cleans the canal effectively with relatively low adverse treatment outcomes. This novel technique, while limited in application, is a safe and effective way to achieve a deep, clean retropreparation.


Testing for respiratory viruses in the neonatal intensive care unit (NICU): Ready for prime time?


title: Disentangling the Frames, the State of Research on the Alphavirus 6K and TF Proteins

text: For 30 years it was thought the alphavirus 6K gene encoded a single 6 kDa protein. However, through a bioinformatics search 10 years ago, it was discovered that there is a frameshifting event and two proteins, 6K and transframe (TF), are translated from the 6K gene. Thus, many functions attributed to the 6K protein needed reevaluation to determine if they properly belong to 6K, TF, or both proteins. In this mini-review, we reevaluate the past research on 6K and put those results in context where there are two proteins, 6K and TF, instead of one. Additionally, we discuss the most cogent outstanding questions for 6K and TF research, including their collective importance in alphavirus budding and their potential importance in disease based on the latest virulence data.


title: Shifts in circulating lymphocyte subsets in cats with feline infectious peritonitis (FIP): pathogenic role and diagnostic relevance

text: Abstract Cats with feline infectious peritonitis (FIP) are usually lymphopenic and have lymphoid depletion evident in spleen and lymph nodes. In particular, the number of CD4+ lymphocytes in tissues decreases during the evolution of FIP lesions. This decrease is most likely due to increased lymphocyte apoptotic rate. In contrast, cats infected with the Feline Coronavirus (FCoV) develop a follicular hyperplasia in the peripheral lymph nodes. The current study was devised to evaluate the possible pathogenic role of shifts in circulating lymphocyte subsets in FIP. Peripheral blood from cats with FIP was evaluated and compared with peripheral blood from clinically healthy cats living in both FCoV-free and FCoV-endemic catteries. Blood from cats with diseases other than FIP was also examined in order to define the diagnostic relevance of the changes. Lymphocyte subsets were analysed by flow cytometry, using a whole blood indirect immunofluorescence technique and mAbs specific for feline CD5, CD4, CD8, CD21. The results of the current study suggest that cats recently infected with FCoV that do not develop the disease have a transient increase in T cells; cats from groups with high prevalence of FIP have a moderate but persistent decrease in T cell subsets; cats with FIP have a very severe decrease in all the subsets of lymphocytes. Moreover, during FIP many lymphocytes do not express any membrane antigen, most likely due to early apoptosis. Cats with diseases other than FIP also had decreased number of lymphocytes: as a consequence, the diagnostic relevance of these findings is very low. Nevertheless, the lack of flow cytometric changes had a high negative predictive value (NPV), thus allowing to exclude FIP from the list of possible diagnoses in cats with normal cytograms.


Kidney biopsy findings in a critically ill COVID-19 patient with dialysis-dependent acute kidney injury: a case against “SARS-CoV-2 nephropathy”


title: Internationalization and the capital structure of firms in emerging markets: Evidence from Latin America before and after the financial crisis

text: Abstract This study examines the impact of internationalization on the capital structure of firms in emerging markets before and after the financial crisis of 2008, with evidence from five countries in Latin America (Argentina, Brazil, Chile, Mexico, and Peru). We find that before the financial crisis, Latin American MNCs are characterized by lower debt levels than purely domestic firms. However, after the financial crisis, we find that the MNCs are characterized by higher debt levels. This finding suggests that after the financial crisis, the Latin American MNCs (like many firms) may be taking advantage of their access to low interest rates in the global capital markets.


title: Prospective observational study in two Dutch hospitals to assess the performance of inflammatory plasma markers to determine disease severity of viral respiratory tract infections in children

text: INTRODUCTION: Respiratory viruses causing lower respiratory tract infections (LRTIs) are a major cause of hospital admissions in children. Since the course of these infections is unpredictable with potential fast deterioration into respiratory failure, infants are easily admitted to the hospital for observation. The aim of this study was to examine whether systemic inflammatory markers can be used to predict severity of disease in children with respiratory viral infections. METHODS: Blood and nasopharyngeal washings from children <3 years of age with viral LRTI attending a hospital were collected within 24 hours (acute) and after 4–6 weeks (recovery). Patients were assigned to a mild (observation only), moderate (supplemental oxygen and/or nasogastric feeding) or severe (mechanical ventilation) group. Linear regression analysis was used to design a prediction rule using plasma levels of C reactive protein (CRP), serum amyloid A (SAA), pentraxin 3 (PTX3), serum amyloid P component and properdin. This rule was tested in a validation cohort. RESULTS: One hundred and four children (52% male) were included. A combination of CRP, SAA, PTX3 and properdin was a better indicator of severe disease compared with any of the individual makers and age (69% sensitivity (95% CI 50 to 83), 90% specificity (95% CI 80 to 96)). Validation in 141 patients resulted in 71% sensitivity (95% CI 53 to 85), 87% specificity (95% CI 79 to 92), negative predictive value of 64% (95% CI 47 to 78) and positive predictive value of 90% (95% CI 82 to 95). The prediction rule was not able to identify patients with a mild course of disease. CONCLUSION: A combination of CRP, SAA, PTX3 and properdin was able to identify children with a severe course of viral LRTI disease, even in children under 2 months of age. To assess the true impact on clinical management, these results should be validated in a prospective randomised control study.


title: Classifying and Summarizing Information from Microblogs During Epidemics

text: During a new disease outbreak, frustration and uncertainties among affected and vulnerable population increase. Affected communities look for known symptoms, prevention measures, and treatment strategies. On the other hand, health organizations try to get situational updates to assess the severity of the outbreak, known affected cases, and other details. Recent emergence of social media platforms such as Twitter provide convenient ways and fast access to disseminate and consume information to/from a wider audience. Research studies have shown potential of this online information to address information needs of concerned authorities during outbreaks, epidemics, and pandemics. In this work, we target three types of end-users (i) vulnerable population—people who are not yet affected and are looking for prevention related information (ii) affected population—people who are affected and looking for treatment related information, and (iii) health organizations—like WHO, who are interested in gaining situational awareness to make timely decisions. We use Twitter data from two recent outbreaks (Ebola and MERS) to build an automatic classification approach useful to categorize tweets into different disease related categories. Moreover, the classified messages are used to generate different kinds of summaries useful for affected and vulnerable communities as well as health organizations. Results obtained from extensive experimentation show the effectiveness of the proposed approach.


COVID-19: underlying metabolic health in the spotlight


title: Agent-based modeling of host–pathogen systems: The successes and challenges

text: Agent-based models have been employed to describe numerous processes in immunology. Simulations based on these types of models have been used to enhance our understanding of immunology and disease pathology. We review various agent-based models relevant to host–pathogen systems and discuss their contributions to our understanding of biological processes. We then point out some limitations and challenges of agent-based models and encourage efforts towards reproducibility and model validation.


title: A new millennium conundrum: how to use a powerful class of influenza anti-neuraminidase drugs (NAIs) in the community

text: Influenza A and B viruses cause serious medical problems and social disruption every year in particular countries of the world. The virus is notoriously fickle and may attack citizens in say two adjacent countries but not the third. More rarely a global pandemic virus emerges causing millions of deaths worldwide. The SARS outbreak has illuminated weaknesses in planning for sudden outbreaks of disease in a modern society and in particular how panic can grip and cause intense economic disruption. Many communities in the world are neither prepared for a global pandemic nor a very acute epidemic of influenza. The neuraminidase inhibitors (NAIs) are a new class of antiviral drug targeting a viral influenza enzyme, the neuraminidase, which acts both to facilitate virus infection of cells by clearing a passage through otherwise protective respiratory fluids and also by helping release of the virus by cutting the chemical umbilical cord which links up the virus to the infected cell. Extensive laboratory studies of the two molecules zanamivir and oseltamivir have shown that they block all influenza A and B viruses yet tested and would, in theory, even inhibit the 1918 pandemic virus. Both drugs can be used prophylactically to prevent spread of infection in families and communities where 80–90% protection has been documented. The therapeutic effects are also strong in adults and children abbreviating infection, reducing quantities of excreted virus and reducing antibiotic prescriptions. The drugs have to be taken within 48 h of the onset of symptoms. Drug resistance is not a problem at present because although such mutants occur the mutants are compromised and are less virulent than their drug-sensitive parents and they spread less easily. The two drugs could be stockpiled to prepare for an influenza pandemic but, importantly, clinical and scientific experience need to be gained by using these inhibitors in the yearly conflagrations of epidemic influenza, which unchecked do great harm to our communities.


title: Severe acute respiratory syndrome (SARS): a review of the history, epidemiology, prevention, and concerns for the future

text: Abstract During the first part of 2003, the world experienced the first epidemic of the 21st century with the emergence of a new and readily transmissible disease. The disease, severe acute respiratory syndrome (SARS), spread quickly and caused numerous deaths, as well as public panic. This article provides a brief review of the initial history of the epidemiology, as well as of the clinical definition, occurrence in the pediatric population, etiology, prevention, drug studies, and considerations for the future.


title: HUMAN CORONAVIRUS DATA FROM FOUR CLINICAL TRIALS OF MASKS AND RESPIRATORS

text: There are few published data on the protection of masks or respirators against coronavirus infections. This is an important research question to inform the response to the COVID-19 epidemic. The transmission modes of human coronaviruses are similar, thought to be by droplet, contact and sometimes airborne routes. There are several randomised clinical trials of masks and respirators, but most used clinical endpoints or tested only for influenza. In four trials which we conducted, we tested for human coronaviruses, but only composite viral endpoints were reported in the trials. We reviewed and analysed the coronavirus data from four of our trials. Laboratory-confirmed coronavirus infections were identified in our community household trial (1 case), health worker trials (8 cases) and trial of mask use by sick patients (19 cases). No coronavirus infections were transmitted in households to parents who wore P2 or surgical masks, but one child with coronavirus infection transmitted infection to a parent in the control arm. No transmissions to close contacts occurred when worn by sick patients with coronavirus infections. There was a higher risk of coronavirus infection in HCWs who wore a mask compared to a respirator, but the difference was not statistically significant. These are the only available data on coronavirus infections associated with mask or respirator use. More clinical trials are needed to assess the efficacy of respiratory protection against coronavirus infections.


title: Chapter 26 Cerebrospinal Fluid

text: Publisher Summary This chapter discusses the anatomy, functions, and biochemistry of cerebrospinal fluid (CSF). CSF has four major functions: physical support of neural structures, excretion and “sink” action, intracerebral transport, and control of the chemical environment of the central nervous system. CSF provides a “water jacket” of physical support and buoyancy. The CSF is protective because its volume changes reciprocally with changes in the volume of intracranial contents, particularly blood. Thus, the CSF protects the brain from changes in arterial and central venous pressure associated with posture, respiration, and exertion. Acute or chronic pathological changes in intracranial contents can be accommodated, to a point, by changes in the CSF volume. The direct transfer of brain metabolites into the CSF provides excretory function. This capacity is important because the brain lacks a lymphatic system. The lymphatic function of the CSF is also manifested in the removal of large proteins and cells, such as bacteria or blood cells, by bulk CSF absorption. The “sink” action of the CSF arises from the restricted access of water-soluble substances to the CSF and the low concentration of these solutes in the CSF.


Social psychological theory and research on the novel coronavirus disease (COVID‐19) pandemic: Introduction to the rapid response special section