title: Multi-omic network signatures of disease

text: To better understand dynamic disease processes, integrated multi-omic methods are needed, yet comparing different types of omic data remains difficult. Integrative solutions benefit experimenters by eliminating potential biases that come with single omic analysis. We have developed the methods needed to explore whether a relationship exists between co-expression network models built from transcriptomic and proteomic data types, and whether this relationship can be used to improve the disease signature discovery process. A naïve, correlation based method is utilized for comparison. Using publicly available infectious disease time series data, we analyzed the related co-expression structure of the transcriptome and proteome in response to SARS-CoV infection in mice. Transcript and peptide expression data was filtered using quality scores and subset by taking the intersection on mapped Entrez IDs. Using this data set, independent co-expression networks were built. The networks were integrated by constructing a bipartite module graph based on module member overlap, module summary correlation, and correlation to phenotypes of interest. Compared to the module level results, the naïve approach is hindered by a lack of correlation across data types, less significant enrichment results, and little functional overlap across data types. Our module graph approach avoids these problems, resulting in an integrated omic signature of disease progression, which allows prioritization across data types for down-stream experiment planning. Integrated modules exhibited related functional enrichments and could suggest novel interactions in response to infection. These disease and platform-independent methods can be used to realize the full potential of multi-omic network signatures. The data (experiment SM001) are publically available through the NIAID Systems Virology (https://www.systemsvirology.org) and PNNL (http://omics.pnl.gov) web portals. Phenotype data is found in the supplementary information. The ProCoNA package is available as part of Bioconductor 2.13.


title: Ezrin Interacts with the SARS Coronavirus Spike Protein and Restrains Infection at the Entry Stage

text: BACKGROUND: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. METHODOLOGY/PRINCIPAL FINDINGS: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S-pseudotyped particles and potentiated S-dependent membrane fusion. CONCLUSIONS/SIGNIFICANCE: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.


title: General thoracic surgery services across Asia during the 2020 COVID-19 pandemic

text: The COVID-19 pandemic of 2020 posed an historic challenge to healthcare systems around the world. Besides mounting a massive response to the viral outbreak, healthcare systems needed to consider provision of clinical services to other patients in need. Surgical services for patients with thoracic disease were maintained to different degrees across various regions of Asia, ranging from significant reductions to near-normal service. Key determinants of robust thoracic surgery service provision included: preexisting plans for an epidemic response, aggressive early action to “flatten the curve”, ability to dedicate resources separately to COVID-19 and routine clinical services, prioritization of thoracic surgery, and the volume of COVID-19 cases in that region. The lessons learned can apply to other regions during this pandemic, and to the world, in preparation for the next one.


Mask‐induced contact dermatitis in handling COVID‐19 outbreak


title: 应用多肽芯片研究非小细胞肺癌患者血清中的EGFR自身抗体

text: BACKGROUND AND OBJECTIVE: Autoantibodies as new tumor markers may play an important role in the early diagnosis and evaluating the prognosis of lung cancer. In this study, we detect epidermal growth factor receptor (EGFR) autoantibodies using peptide array and screen the epitopes which are recognized by EGFR autoantibodies. METHODS: Peptide array covering the extracellular domain of EGFR protein was synthesized by a synthesizer (ASPSL) made by Intavis company. EGFR autoantibodies in the serums of non-small cell lung cancer patients was detected using peptide array. RESULTS: Six of 20 patients were found to have EGFR autoantibodis. The positive rate is 30%. Nine high frequency spots were found in the 6 positive patients and 8 high frequency spots clustered in the Ⅲ and Ⅳ domains. CONCLUSION: These findings will offer new clues for the futher studies of EGFR and EGFR autoantibodies.


title: Molecular detection and characterization of human gyroviruses identified in the ferret fecal virome

text: The recently described novel gyroviruses may infect chickens and/or humans; however, their pathogenic potential is unknown. In our metagenomic investigation, we detected many of the novel gyroviruses in the fecal viromes of ferrets with lymph node and organ enlargement. The complete genomic sequences of selected gyrovirus strains showed 90.7-99.4 % similarity to homologous reference gyrovirus strains. This study did not demonstrate an association between gyrovirus shedding from ferrets and the observed background disease; however, it provides evidence for genetic diversity among gyroviruses and raises the possibility that pet ferrets may transmit gyroviruses to heterologous hosts, e.g., humans.


title: The added value of pirfenidone to fight inflammation and fibrotic state induced by SARS-CoV-2: Anti-inflammatory and anti-fibrotic therapy could solve the lung complications of the infection?

text: AIM: SARS-CoV-2 infection has been divided by scientific opinion into three phases: the first as asymptomatic or slightly symptomatic and the second and the third with greater severity, characterized by a hyperinflammatory and fibrotic state, responsible for lung lesions, in some cases fatal. The development of antiviral drugs directed against SARS-CoV-2 and effective vaccines is progressing; meanwhile, the best pharmacological objective is related to the management of all the complications caused by this viral infection, mainly controlling the inflammatory and fibrotic state and preventing the infection from moving into the most serious phases. SUBJECT AND METHOD: Describe the scientific rationale related to the use of an antifibrotic therapy with pirfenidone, as monotherapy and/or in combination with anti-inflammatory drugs to manage and control complications of SARS-CoV-2 infection. RESULTS: Based on the scientific literature and epidemiological results and considering the pathophysiological, biological, and molecular characteristics of SARS-CoV-2, an antifibrotic drug such as pirfenidone as monotherapy or in combination with anti-inflammatory drugs can be (acting early, at the right doses and at the right time) therapeutically effective to avoid serious complications during viral infection. The same approach can also be effective as postinfection therapy in patients with residual pulmonary fibrotic damage. Management of inflammation and fibrotic status with a combination therapy of pirfenidone and IL-6 or IL-1 inhibitors could represent a pharmacological synergy with added value. CONCLUSION: In this article, we consider the role of antifibrotic therapy with pirfenidone in patients with SARS-CoV-2 infection on going or in the stage of postinfection with pulmonary fibrotic consequences. The scientific rationale for its use is also described.


title: Airflow Dynamics of Coughing in Healthy Human Volunteers by Shadowgraph Imaging: An Aid to Aerosol Infection Control

text: Cough airflow dynamics have been previously studied using a variety of experimental methods. In this study, real-time, non-invasive shadowgraph imaging was applied to obtain additional analyses of cough airflows produced by healthy volunteers. Twenty healthy volunteers (10 women, mean age 32.2±12.9 years; 10 men, mean age 25.3±2.5 years) were asked to cough freely, then into their sleeves (as per current US CDC recommendations) in this study to analyze cough airflow dynamics. For the 10 females (cases 1–10), their maximum detectable cough propagation distances ranged from 0.16–0.55 m, with maximum derived velocities of 2.2–5.0 m/s, and their maximum detectable 2-D projected areas ranged from 0.010–0.11 m(2), with maximum derived expansion rates of 0.15–0.55 m(2)/s. For the 10 males (cases 11–20), their maximum detectable cough propagation distances ranged from 0.31–0.64 m, with maximum derived velocities of 3.2–14 m/s, and their maximum detectable 2-D projected areas ranged from 0.04–0.14 m(2), with maximum derived expansion rates of 0.25–1.4 m(2)/s. These peak velocities were measured when the visibility of the exhaled airflows was optimal and compare favorably with those reported previously using other methods, and may be seen as a validation of these previous approaches in a more natural setting. However, the propagation distances can only represent a lower limit due to the inability of the shadowgraph method to visualize these cough airflows once their temperature cools to that of the ambient air, which is an important limitation of this methodology. The qualitative high-speed video footage of these volunteers coughing into their sleeves demonstrates that although this method rarely completely blocks the cough airflow, it decelerates, splits and redirects the airflow, eventually reducing its propagation. The effectiveness of this intervention depends on optimum positioning of the arm over the nose and mouth during coughing, though unsightly stains on sleeves may make it unacceptable to some.


title: Social Capital and Sleep Quality in Individuals Who Self-Isolated for 14 Days During the Coronavirus Disease 2019 (COVID-19) Outbreak in January 2020 in China

text: BACKGROUND: From the end of December 2019, coronavirus disease 2019 (COVID-19) began to spread in central China. Social capital is a measure of social trust, belonging, and participation. This study aimed to investigate the effects of social capital on sleep quality and the mechanisms involved in people who self-isolated at home for 14 days in January 2020 during the COVID-19 epidemic in central China. METHODS: Individuals (n=170) who self-isolated at home for 14 days in central China, completed self-reported questionnaires on the third day of isolation. Individual social capital was assessed using the Personal Social Capital Scale 16 (PSCI-16) questionnaire. Anxiety was assessed using the Self-Rating Anxiety Scale (SAS) questionnaire, stress was assessed using the Stanford Acute Stress Reaction (SASR) questionnaire, and sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Path analysis was performed to evaluate the relationships between a dependent variable (social capital) and two or more independent variables, using Pearson’s correlation analysis and structural equation modeling (SEM). RESULTS: Low levels of social capital were associated with increased levels of anxiety and stress, but increased levels of social capital were positively associated with increased quality of sleep. Anxiety was associated with stress and reduced sleep quality, and the combination of anxiety and stress reduced the positive effects of social capital on sleep quality. CONCLUSION: During a period of individual self-isolation during the COVID-19 virus epidemic in central China, increased social capital improved sleep quality by reducing anxiety and stress.


title: Why does the number of dangerous species of scorpions increase? The particular case of the genus Leiurus Ehrenberg (Buthidae) in Africa

text: The aim of this contribution is to bring some precise information on the reasons why the number of noxious scorpion species is constantly growing. This fact is directly associated with the zoological research on the domains generally defined as systematics and taxonomy. The classification of any zoological group is in most cases a source of problem for most biologists not directly involved with this almost confidential aspect of the zoological research. Much information has been gathered and published over two centuries on the classification but it is remains poorly accessible and too technical for non-experts. The exposed example could be taken from several groups of scorpions possessing infamous species, but the choice went to the genus Leiurus Ehrenberg, 1828 distributed from North Africa to the Middle East. Maybe this contribution will help to explain why so numerous cases of species misidentification are regularly present in the general literature devoted to scorpion venoms and incidents.


title: The RNA Helicase DDX6 Associates with RIG-I to Augment Induction of Antiviral Signaling

text: Virus infections induce sensitive antiviral responses within the host cell. The RNA helicase retinoic acid-inducible gene I (RIG-I) is a key sensor of influenza virus RNA that induces the expression of antiviral type I interferons. Recent evidence suggests a complex pattern of RIG-I regulation involving multiple interactions and cellular sites. In an approach employing affinity purification and quantitative mass spectrometry, we identified proteins with increased binding to RIG-I in response to influenza B virus infection. Among them was the RIG-I related RNA helicase DEAD box helicase 6 (DDX6), a known component of cytoplasmic mRNA-ribonucleoprotein (mRNP) granules like P-bodies and stress granules (SGs). RIG-I and DDX6 both localized to the cytosol and were detected in virus-induced SGs. Coimmunoprecipitation assays detected a basal level of complexes harboring RIG-I and DDX6 that increased after infection. Functionally, DDX6 augmented RIG-I mediated induction of interferon (IFN)-β expression. Notably, DDX6 was found to bind viral RNA capable to stimulate RIG-I. These findings imply a novel function for DDX6 as an RNA co-sensor and signaling enhancer for RIG-I.


docid: mcyiqrws

title: SARS‐CoV‐2 infection in beta thalassemia: Preliminary data from the Italian experience


title: Picoliter Well Array Chip-Based Digital Recombinase Polymerase Amplification for Absolute Quantification of Nucleic Acids

text: Absolute, precise quantification methods expand the scope of nucleic acids research and have many practical applications. Digital polymerase chain reaction (dPCR) is a powerful method for nucleic acid detection and absolute quantification. However, it requires thermal cycling and accurate temperature control, which are difficult in resource-limited conditions. Accordingly, isothermal methods, such as recombinase polymerase amplification (RPA), are more attractive. We developed a picoliter well array (PWA) chip with 27,000 consistently sized picoliter reactions (314 pL) for isothermal DNA quantification using digital RPA (dRPA) at 39°C. Sample loading using a scraping liquid blade was simple, fast, and required small reagent volumes (i.e., <20 μL). Passivating the chip surface using a methoxy-PEG-silane agent effectively eliminated cross-contamination during dRPA. Our creative optical design enabled wide-field fluorescence imaging in situ and both end-point and real-time analyses of picoliter wells in a 6-cm(2) area. It was not necessary to use scan shooting and stitch serial small images together. Using this method, we quantified serial dilutions of a Listeria monocytogenes gDNA stock solution from 9 × 10(-1) to 4 × 10(-3) copies per well with an average error of less than 11% (N = 15). Overall dRPA-on-chip processing required less than 30 min, which was a 4-fold decrease compared to dPCR, requiring approximately 2 h. dRPA on the PWA chip provides a simple and highly sensitive method to quantify nucleic acids without thermal cycling or precise micropump/microvalve control. It has applications in fast field analysis and critical clinical diagnostics under resource-limited settings.


title: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) origin and animal reservoir

text: Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans. Though not confirmed yet, multiple surveillance and phylogenetic studies suggest a bat origin. The disease is heavily endemic in dromedary camel populations of East Africa and the Middle East. It is unclear as to when the virus was introduced to dromedary camels, but data from studies that investigated stored dromedary camel sera and geographical distribution of involved dromedary camel populations suggested that the virus was present in dromedary camels several decades ago. Though bats and alpacas can serve as potential reservoirs for MERS-CoV, dromedary camels seem to be the only animal host responsible for the spill over human infections.


title: Exhaled Air Dispersion during Coughing with and without Wearing a Surgical or N95 Mask

text: OBJECTIVES: We compared the expelled air dispersion distances during coughing from a human patient simulator (HPS) lying at 45° with and without wearing a surgical mask or N95 mask in a negative pressure isolation room. METHODS: Airflow was marked with intrapulmonary smoke. Coughing bouts were generated by short bursts of oxygen flow at 650, 320, and 220L/min to simulate normal, mild and poor coughing efforts, respectively. The coughing jet was revealed by laser light-sheet and images were captured by high definition video. Smoke concentration in the plume was estimated from the light scattered by smoke particles. Significant exposure was arbitrarily defined where there was ≥ 20% of normalized smoke concentration. RESULTS: During normal cough, expelled air dispersion distances were 68, 30 and 15 cm along the median sagittal plane when the HPS wore no mask, a surgical mask and a N95 mask, respectively. In moderate lung injury, the corresponding air dispersion distances for mild coughing efforts were reduced to 55, 27 and 14 cm, respectively, p < 0.001. The distances were reduced to 30, 24 and 12 cm, respectively during poor coughing effort as in severe lung injury. Lateral dispersion distances during normal cough were 0, 28 and 15 cm when the HPS wore no mask, a surgical mask and a N95 mask, respectively. CONCLUSIONS: Normal cough produced a turbulent jet about 0.7 m towards the end of the bed from the recumbent subject. N95 mask was more effective than surgical mask in preventing expelled air leakage during coughing but there was still significant sideway leakage.


title: Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits

text: Middle East respiratory syndrome coronavirus (MERS-CoV) transmission from dromedaries to humans has resulted in major outbreaks in the Middle East. Although some other livestock animal species have been shown to be susceptible to MERS-CoV, it is not fully understood why the spread of the virus in these animal species has not been observed in the field. In this study, we used rabbits to further characterize the transmission potential of MERS-CoV. In line with the presence of MERS-CoV receptor in the rabbit nasal epithelium, high levels of viral RNA were shed from the nose following virus inoculation. However, unlike MERS-CoV-infected dromedaries, these rabbits did not develop clinical manifestations including nasal discharge and did shed only limited amounts of infectious virus from the nose. Consistently, no transmission by contact or airborne routes was observed in rabbits. Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission.


title: COVID-19 Outbreak Among Three Affiliated Homeless Service Sites — King County, Washington, 2020

text: On March 30, 2020, Public Health - Seattle and King County (PHSKC) was notified of a confirmed case of coronavirus disease 2019 (COVID-19) in a resident of a homeless shelter and day center (shelter A). Residents from two other homeless shelters (B and C) used shelter A's day center services. Testing for SARS-CoV-2, the virus that causes COVID-19, was offered to available residents and staff members at the three shelters during March 30-April 1, 2020. Among the 181 persons tested, 19 (10.5%) had positive test results (15 residents and four staff members). On April 1, PHSKC and CDC collaborated to conduct site assessments and symptom screening, isolate ill residents and staff members, reinforce infection prevention and control practices, provide face masks, and advise on sheltering-in-place. Repeat testing was offered April 7-8 to all residents and staff members who were not tested initially or who had negative test results. Among the 118 persons tested in the second round of testing, 18 (15.3%) had positive test results (16 residents and two staff members). In addition to the 31 residents and six staff members identified through testing at the shelters, two additional cases in residents were identified during separate symptom screening events, and four were identified after two residents and two staff members independently sought health care. In total, COVID-19 was diagnosed in 35 of 195 (18%) residents and eight of 38 (21%) staff members who received testing at the shelter or were evaluated elsewhere. COVID-19 can spread quickly in homeless shelters; rapid interventions including testing and isolation to identify cases and minimize transmission are necessary. CDC recommends that homeless service providers implement appropriate infection control practices, apply physical distancing measures including ensuring resident's heads are at least 6 feet (2 meters) apart while sleeping, and promote use of cloth face coverings among all residents (1).


title: ‘Africanisation’ of South Africa’s international air links, 1994–2003

text: Abstract In the first decade of democratic rule in South Africa scheduled commercial passenger flights across the country’s borders more than doubled. Additional flights served new African air passenger markets and secondary airports in established markets. Overseas flights increased more slowly, serving a diminishing number of overseas countries and cities. In 1994 the Republic was linked directly by air with more overseas than African countries and cities; within a decade the pattern reversed. The changing geography of South Africa’s international air links reflects developments in the international airline industry, and South Africa’s increasingly prominent political and commercial role in Africa.


title: Identification of VP1 peptides diagnostic of encephalomyocarditis virus from swine

text: BACKGROUND: Encephalomyocarditis virus (EMCV) can cause myocarditis, respiratory failure, reproductive failure, and sudden death in pre-weaned piglets, which has been isolated in China. EMCV VP1 protein was one of the most important structural proteins and played an important role in the protective immunity. In this study, 10 monoclonal antibodies (McAbs) against EMCV VP1 were screened and identified. RESULTS: Epitope mapping results indicated that McAbs (6E11, 7A7, 7C9) specifically recognized the linear epitopes V(2)ENAEK(7), McAbs (1D1, 2A2, 5A1, 5A11, 5G1) recognized the epitope F(19)VAQPVY(25), and McAbs 1G8 and 3A9 recognized P(42)IGAFTVK(49). Protein sequence alignment of VP1 with 16 EMCV isolates indicated that the epitope F(19)VAQPVY(25) was conserved in all the reference strains. The epitopes P(42)IGAFTVK(49) and V(2)ENAEK(7) only had 1 or 2 variable amino acid among the reference strains. The 3D model analysis results showed that these epitopes presented as spheres were shown within the context of the complete particle. CONCLUSIONS: In this study, ten McAbs against EMCV VP1 were developed and three B-cells epitopes (2-7aa, 19-25aa and 42-49aa) were defined in VP1. All the results herein will promote the future investigations into the function of VP1 of EMCV and development of diagnostic methods of EMCV.


title: Viral Regulation of RNA Granules in Infected Cells

text: RNA granules are cytoplasmic, microscopically visible, non-membrane ribo-nucleoprotein structures and are important posttranscriptional regulators in gene expression by controlling RNA translation and stability. TIA/G3BP/PABP-specific stress granules (SG) and GW182/DCP-specific RNA processing bodies (PB) are two major distinguishable RNA granules in somatic cells and contain various ribosomal subunits, translation factors, scaffold proteins, RNA-binding proteins, RNA decay enzymes and helicases to exclude mRNAs from the cellular active translational pool. Although SG formation is inducible due to cellular stress, PB exist physiologically in every cell. Both RNA granules are important components of the host antiviral defense. Virus infection imposes stress on host cells and thus induces SG formation. However, both RNA and DNA viruses must confront the hostile environment of host innate immunity and apply various strategies to block the formation of SG and PB for their effective infection and multiplication. This review summarizes the current research development in the field and the mechanisms of how individual viruses suppress the formation of host SG and PB for virus production.


title: Serologic Evidence for Influenza C and D Virus among Ruminants and Camelids, Africa, 1991–2015

text: Influenza D virus has been identified in America, Europe, and Asia. We detected influenza D virus antibodies in cattle and small ruminants from North (Morocco) and West (Togo and Benin) Africa. Dromedary camels in Kenya harbored influenza C or D virus antibodies, indicating a potential new host for these viruses.


Editor’s Desk


African perspectives: modern complexities of emerging, re-emerging, and endemic zoonoses


title: Vitamin D and Immunity in Infants and Children

text: The last couple of decades have seen an explosion in our interest and understanding of the role of vitamin D in the regulation of immunity. At the molecular level, the hormonal form of vitamin D signals through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor. The VDR and vitamin D metabolic enzymes are expressed throughout the innate and adaptive arms of the immune system. The advent of genome-wide approaches to gene expression profiling have led to the identification of numerous VDR-regulated genes implicated in the regulation of innate and adaptive immunity. The molecular data infer that vitamin D signaling should boost innate immunity against pathogens of bacterial or viral origin. Vitamin D signaling also suppresses inflammatory immune responses that underlie autoimmunity and regulate allergic responses. These findings have been bolstered by clinical studies linking vitamin D deficiency to increased rates of infections, autoimmunity, and allergies. Our goals here are to provide an overview of the molecular basis for immune system regulation and to survey the clinical data from pediatric populations, using randomized placebo-controlled trials and meta-analyses where possible, linking vitamin D deficiency to increased rates of infections, autoimmune conditions, and allergies, and addressing the impact of supplementation on these conditions.


Systems Biology Brings Life Sciences Closer: —Report on the China-UK Systems Biology Workshop 2005


title: Engineering Immunity in the Mammary Gland

text: The major physiological function of milk is the transport of amino acids, carbohydrates, lipids, and minerals to mammalian offspring. However, milk is also a rich collection of antimicrobial substances, which provide protection against pathogenic infections. These molecules safeguard the integrity of the lactating mammary gland, but also provide protection for the suckling offspring during a time when its immune system is still immature. The protective substances can be classified into two categories: 1) nonspecific defense substances, which provide innate immunity, and 2) molecules such as antibodies, which provide adaptive immunity and are directed against specific pathogens. The antimicrobial potency of milk has not been a target for farm animal breeding in the past, and present day ruminants provide suboptimal levels of antimicrobial substances in milk. Altered breeding regimes, pharmacological intervention, and transgenesis can be utilized to improve the antimicrobial properties of milk. Such alterations of milk composition have implications for human and animal health.


docid: vkebrwgf

title: Characterization of Viral Agents Causing Acute Respiratory Infection in a San Francisco University Medical Center Clinic during the Influenza Season

text: Background. With use of polymerase chain reaction (PCR) and a centrifugation-enhanced viral culture method, we characterized the viruses causing acute respiratory infection in adults during an influenza season. Methods. During January-March 2002, nasopharyngeal wash specimens from previously healthy adults presenting with respiratory symptoms were evaluated for viral pathogens with centrifugation-enhanced viral culture and PCR. Results The diagnoses in 266 cases included unspecified upper respiratory infection (in 142 [54%] of the cases), acute bronchitis (42 [16%]), sinusitis (23 [9%]), pharyngitis (22 [8%]), and pneumonia (17 [6%]). The use of a shell vial assay and PCR identified a pathogen in 103 (39%) of the patients, including influenza A or B in 54, picornavirus in 28 (including rhinovirus in 24), respiratory syncytial virus (RSV) in 12, human metapneumovirus in 4, human coronavirus OC43 in 2, adenovirus in 2, parainfluenza virus type 1 in 1, and coinfection with influenza and parainfluenza virus type 1 in 2. Conclusion. Our findings demonstrate that, even during the influenza season, rhinovirus and RSV are prevalent and must be considered in the differential diagnosis of adult acute respiratory infection before prescribing antiviral medication. Human coronavirus and human metapneumovirus did not play a substantial role. PCR was an especially useful tool in the identification of influenza and other viral pathogens not easily detected by traditional testing methods.


title: Severe Acute Respiratory Syndrome Coronavirus on Hospital Surfaces

text: Background. Health care workers continued to contract severe acute respiratory syndrome (SARS), even after barrier precautions were widely implemented. Methods. We explored the possible contribution of contaminated hospital surfaces to SARS transmission by swabbing surfaces in 2 hospitals and testing the swab samples by reverse-transcriptase polymerase chain reaction (RT-PCR) and viral culture. Results. Twenty-six of 94 swab samples tested positive for viral RNA. Swab samples of respiratory secretions from each of the 4 patients examined tested positive by RT-PCR, as were 12 of 43 swabs from patient rooms and 10 of 47 swabs from other parts of the hospital, including the computer mouses at 2 nursing stations and the handrail of the public elevator. Specimens from areas with patients with SARS in the most infectious phase of illness (days 5–15 after onset) were more likely to be RNA positive than were swab specimens from elsewhere (24 of 63 samples vs. 2 of 31 samples; P = .001). All cultures showed no growth. Conclusions. Although the viruses identified may have been noninfectious, health care workers should be aware that SARS coronavirus can contaminate environmental surfaces in the hospital, and fomites should be considered to be a possible mode of transmission of SARS.


docid: lkhmgfnc

title: SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression

text: Since the WHO declared COVID-19 a pandemic, a great effort has been made to understand this serious disease. Thousands of studies are being devoted to understanding its epidemiology, its molecular characteristics, its mechanisms, and the clinical evolution of this viral infection. However, little has been published on its pathogenesis and the host response mechanisms in the progress of the disease. Therefore, we propose a hypothesis based on strong scientific documentation, associating oxidative stress with changes found in patients with COVID-19, such as its participation in the amplification and perpetuation of the cytokine storm, coagulopathy, and cell hypoxia. Finally, we suggest a therapeutic strategy to reduce oxidative stress using antioxidants, NFkB inhibitors, Nrf2 activators, and iron complexing agents. We believe that this hypothesis can guide new studies and therapeutic strategies on this topic.


title: SKEMPI 2.0: An updated benchmark of changes in protein-protein binding energy, kinetics and thermodynamics upon mutation

text: Understanding the relationship between the sequence, structure, binding energy, binding kinetics and binding thermodynamics of protein-protein interactions is crucial to understanding cellular signaling, the assembly and regulation of molecular complexes, the mechanisms through which mutations lead to disease, and protein engineering. We present SKEMPI 2.0, a major update to our database of binding free energy changes upon mutation for structurally resolved protein-protein interactions. This version now contains manually curated binding data for 7085 mutations, an increase of 133%, including changes in kinetics for 1844 mutations, enthalpy and entropy changes for 443 mutations, and 440 mutations which abolish detectable binding. The database is available at https://life.bsc.es/pid/skempi2/


title: ''Determining Host Factors Contributing to Disease Severity in a Family Cluster of 29 Hospitalized SARS‐CoV‐2 Patients: Could Genetic Factors Be Relevant in the Clinical Course of COVID‐19?''

text: OBJECTIVE: In this study, we report a large family cluster consisting of 29 genetically related patients hospitalized with COVID‐19. We sought to determine the clinical characteristics relevant to the clinical course of COVID‐19 by comparing the family cluster to unrelated patients with SARS‐CoV‐2 infection so that the presence of potential determinants of disease severity, other than traditional risk factors previously reported, could be investigated. METHODS: 29 patient files were investigated in Group 1 and Group 2 was created with 52 consecutive COVID‐19 patients with age and gender compatibility. The virus was detected for diagnosis. The clinical, laboratory and imaging features of all patients were retrospectively screened. Disease course was assessed using records regarding outcome from patient files retrospectively. Groups were compared with respect to baseline characteristics, disease severity on presentation, disease course. RESULTS: There was no difference between the two groups in terms of comorbidity and smoking history. In terms of in‐hospital treatment, use differed not significantly between two groups. We found that all 29 patients in Group 1 had severe pneumonia, 18 patients had severe pneumonia. Hospitalization rates, length of hospital stay and transferred to ICU were found to be statistically significantly higher in Group 1. CONCLUSION: In the present study, COVID‐19 cases in the large family cluster were shown to have more severe disease and worse clinical course compared to consecutive COVID‐19 patients presenting to the same time. We believe further studies into potential genetic mechanisms of host susceptibility to COVID‐19 should include such family clusters. This article is protected by copyright. All rights reserved.


title: Obesity predisposes to the risk of higher mortality in young COVID‐19 patients

text: BACKGROUND: Although emerging data demonstrated mortality of young COVID‐19 patients, but no data reported the risk factors of mortality for those young patients, and whether obesity is a risk for young COVID‐19 patients remains unknown. METHODS: We conducted a retrospective study including 13 young patients died of COVID‐19 and 40 matched survivors. Logistic regression was employed to characterize the risk factors of mortality in young obese COVID‐19 patients. RESULTS: Most of the young deceased COVID‐19 patients were mild cases at the time of admission, but the disease progressed rapidly featured by the higher severity of Patchy shadows (100.00% vs. 48.70%, P = 0.006), pleural thickening (61.50% vs. 12.80%, P = 0.012), mild pericardial effusion (76.90% vs. 0.00%, P < 0.001). Most importantly, the deceased patients manifested higher BMI (OR = 1.354, 95% CI = 1.075‐1.704, P = 0.010), inflammatory‐related index CRP (OR = 1.014, 95% CI = 1.003‐1.025, P = 0.014), cardiac injury biomarker hs‐cTnI (OR = 1.420, 95% CI = 1.112‐1.814, P = 0.005), and increased coagulation activity biomarker D‐Dimer (OR = 418.7, P = 0.047), as compared to that of survivors. CONCLUSIONS: Our data support that obesity could be a risk factor associated with high mortality in young COVID‐19 patients, while aggravated inflammatory response, enhanced cardiac injury and increased coagulation activity are likely to be the mechanisms contributing to the high mortality. This article is protected by copyright. All rights reserved.


Covid‐19 and urology


title: Clinical outcomes among hospital patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection

text: BACKGROUND: Mortality is high among patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. We aimed to determine hospital mortality and the factors associated with it in a cohort of MERS-CoV patients. METHODS: We reviewed hospital records of confirmed cases (detection of virus by polymerase chain reaction from respiratory tract samples) of MERS-CoV patients (n = 63) admitted to Buraidah Central Hospital in Al-Qassim, Saudi Arabia between 2014 and 2017. We abstracted data on demography, vital signs, associated conditions presented on admission, pre-existing chronic diseases, treatment, and vital status. Bi-variate comparisons and multiple logistic regressions were the choice of data analyses. RESULTS: The mean age was 60 years (SD = 18.2); most patients were male (74.6%) and Saudi citizens (81%). All but two patients were treated with Ribavirin plus Interferon. Hospital mortality was 25.4%. Patients who were admitted with septic shock and/or organ failure were significantly more likely to die than patients who were admitted with pneumonia and/or acute respiratory distress syndrome (OR = 47.9, 95% CI = 3.9, 585.5, p-value 0.002). Age, sex, and presence of chronic conditions were not significantly associated with mortality. CONCLUSION: Hospital mortality was 25%; septic shock/organ failure at admittance was a significant predictor of mortality.


title: RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines

text: BACKGROUND: Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced “RNA disruption” is, the extent to which it is associated with drug response or what the underlying mechanisms are. METHODS: Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. RESULTS: All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3’-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. CONCLUSIONS: Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues and is associated with drug response. Although present, the link between apoptosis and RNA disruption is not completely understood. Evaluation of RNA disruption is thus proposed as a novel and effective biomarker to assess response to chemotherapy drugs in vitro and in vivo. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2197-1) contains supplementary material, which is available to authorized users.


title: The multifarious roles of heterogeneous ribonucleoprotein A1 in viral infections

text: Viruses are obligate parasites known to interact with a wide variety of host proteins at different stages of infection. Current antiviral treatments target viral proteins and may be compromised due to the emergence of drug resistant viral strains. Targeting viral‐host interactions is now gaining recognition as an alternative approach against viral infections. Recent research has revealed that heterogeneous ribonucleoprotein A1, an RNA‐binding protein, plays an essential functional and regulatory role in the life cycle of many viruses. In this review, we summarize the interactions between heterogeneous ribonucleoprotein A1 (hnRNPA1) and multiple viral proteins during the life cycle of RNA and DNA viruses. hnRNPA1 protein levels are modulated differently, in different viruses, which further dictates its stability, function, and intracellular localization. Multiple reports have emphasized that in Sindbis virus, enteroviruses, porcine endemic diarrhea virus, and rhinovirus infection, hnRNPA1 enhances viral replication and survival. However, in others like hepatitis C virus and human T‐cell lymphotropic virus, it exerts a protective response. The involvement of hnRNPA1 in viral infections highlights its importance as a central regulator of host and viral gene expression. Understanding the nature of these interactions will increase our understanding of specific viral infections and pathogenesis and eventually aid in the development of novel and robust antiviral intervention strategies.


Challenges in the Care of IBD Patients During the CoViD-19 Pandemic: Report From a “Red Zone” Area in Northern Italy


title: Prioritization of livestock transboundary diseases in Belgium using a multicriteria decision analysis tool based on drivers of emergence

text: During the past decade, livestock diseases have (re‐)emerged in areas where they had been previously eradicated or never been recorded before. Drivers (i.e. factors of (re‐)emergence) have been identified. Livestock diseases spread irrespective of borders, and therefore, reliable methods are required to help decision‐makers to identify potential threats and try stopping their (re‐)emergence. Ranking methods and multicriteria approaches are cost‐effective tools for such purpose and were applied to prioritize a list of selected diseases (N = 29 including 6 zoonoses) based on the opinion of 62 experts in accordance with 50 drivers‐related criteria. Diseases appearing in the upper ranking were porcine epidemic diarrhoea, foot‐and‐mouth disease, low pathogenic avian influenza, African horse sickness and highly pathogenic avian influenza. The tool proposed uses a multicriteria decision analysis approach to prioritize pathogens according to drivers and can be applied to other countries or diseases.


title: Single-dose replicating RNA vaccine induces neutralizing antibodies against SARS-CoV-2 in nonhuman primates

text: The ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and deleterious impact on health services and the global economy. Grim public health statistics highlight the need for vaccines that can rapidly confer protection after a single dose and be manufactured using components suitable for scale-up and efficient distribution. In response, we have rapidly developed repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, delivery and immunogenicity. We show that intramuscular injection of LION/repRNA-CoV2S elicits robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as well as potent T cell responses in mice. Importantly, a single-dose administration in nonhuman primates elicited antibody responses that potently neutralized SARS-CoV-2. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-2 infection.


title: Use of ward closure to control outbreaks among hospitalized patients in acute care settings: a systematic review

text: BACKGROUND: Though often used to control outbreaks, the efficacy of ward closure is unclear. This systematic review sought to identify studies defining and describing ward closure in outbreak control and to determine impact of ward closure as an intervention on outbreak containment. METHODS: We searched these databases with no language restrictions: MEDLINE, 1946 to 7 July 2014; EMBASE, 1974 to 7 July 2014; CINAHL, 1937 to 8 July 2014; and Cochrane Database of Systematic Reviews, 2005 to May 2014. We also searched the following: IndMED; LILACS; reference lists from retrieved articles; conference proceedings; and websites of the CDCP, the ICID, and the WHO. We included studies of patients hospitalized in acute care facilities; used ward closure as a control measure; used other control measures; and discussed control of the outbreak(s) under investigation. A component approach was used to assess study quality. RESULTS: We included 97 English and non-English observational studies. None included a controlled comparison between ward closure and other interventions. We found that ward closure was often used as part of a bundle of interventions but could not determine its direct impact separate from all the other interventions whether used in parallel or in sequence with other interventions. We also found no universal definition of ward closure which was widely accepted. CONCLUSIONS: With no published controlled studies identified, ward closure for control of outbreaks remains an intervention that is not evidence based and healthcare personnel will need to continue to balance the competing risks associated with its use, taking into consideration the nature of the outbreak, the type of pathogen and its virulence, mode of transmission, and the setting in which it occurs. Our review has identified a major research gap in this area. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13643-015-0131-2) contains supplementary material, which is available to authorized users.


title: Development of a recombinant Newcastle disease virus-vectored vaccine for infectious bronchitis virus variant strains circulating in Egypt

text: Infectious bronchitis virus (IBV) causes a major disease problem for the poultry industry worldwide. The currently used live-attenuated vaccines have the tendency to mutate and/or recombine with circulating field strains resulting in the emergence of vaccine-derived variant viruses. In order to circumvent these issues, and to develop a vaccine that is more relevant to Egypt and its neighboring countries, a recombinant avirulent Newcastle disease virus (rNDV) strain LaSota was constructed to express the codon-optimized S glycoprotein of the Egyptian IBV variant strain IBV/Ck/EG/CU/4/2014 belonging to GI-23 lineage, that is prevalent in Egypt and in the Middle East. A wild type and two modified versions of the IBV S protein were expressed individually by rNDV. A high level of S protein expression was detected in vitro by Western blot and immunofluorescence analyses. All rNDV-vectored IBV vaccine candidates were genetically stable, slightly attenuated and showed growth patterns comparable to that of parental rLaSota virus. Single-dose vaccination of 1-day-old SPF White Leghorn chicks with the rNDVs expressing IBV S protein provided significant protection against clinical disease after IBV challenge but did not show reduction in tracheal viral shedding. Single-dose vaccination also provided complete protection against virulent NDV challenge. However, prime-boost vaccination using rNDV expressing the wild type IBV S protein provided better protection, after IBV challenge, against clinical signs and significantly reduced tracheal viral shedding. These results indicate that the NDV-vectored IBV vaccines are promising bivalent vaccine candidates to control both infectious bronchitis and Newcastle disease in Egypt. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13567-019-0631-5) contains supplementary material, which is available to authorized users.


title: Angiotensin-converting enzyme 2 and new insights into the renin–angiotensin system

text: Abstract Components of the renin–angiotensin system are well established targets for pharmacological intervention in a variety of disorders. Many such therapies abrogate the effects of the hypertensive and mitogenic peptide, angiotensin II, by antagonising its interaction with its receptor, or by inhibiting its formative enzyme, angiotensin-converting enzyme (ACE). At the turn of the millennium, a homologous enzyme, termed ACE2, was identified which increasingly shares the limelight with its better-known homologue. In common with ACE, ACE2 is a type I transmembrane metallopeptidase; however, unlike ACE, ACE2 functions as a carboxypeptidase, cleaving a single C-terminal residue from a distinct range of substrates. One such substrate is angiotensin II, which is hydrolysed by ACE2 to the vasodilatory peptide angiotensin 1–7. In this commentary we discuss the latest developments in the rapidly progressing study of the physiological and patho-physiological roles of ACE2 allied with an overview of the current understanding of its molecular and cell biology. We also discuss parallel developments in the study of collectrin, a catalytically inactive homologue of ACE2 with critical functions in the pancreas and kidney.


title: Ethnoveterinary medicines used for horses in Trinidad and in British Columbia, Canada

text: This paper investigates the commonalities in ethnoveterinary medicine used for horses between Trinidad (West Indies) and British Columbia (Canada). These research areas are part of a common market in pharmaceuticals and are both involved in the North American racing circuit. There has been very little research conducted on medicinal plants used for horses although their use is widespread. The data on ethnoveterinary medicines used for horses was obtained through key informant interviews with horse owners, trainers, breeders, jockeys, grooms and animal care specialists in two research areas: Trinidad and British Columbia (BC). A participatory validation workshop was held in BC. An extensive literature review and botanical identification of the plants was also done. In all, 20 plants were found to be used in treating racehorses in Trinidad and 97 in BC. Of these the most-evidently effective plants 19 of the plants used in Trinidad and 66 of those used in BC are described and evaluated in this paper. Aloe vera, Curcuma longa and Ricinus communis are used in both research areas. More research is needed in Trinidad to identify plants that respondents claimed were used in the past. Far more studies have been conducted on the temperate and Chinese medicinal plants used in BC and therefore these ethnoveterinary remedies reflect stronger evidence of efficacy.


title: Stereoselective synthesis of trans-dihydronarciclasine derivatives containing a 1,4-benzodioxane moiety

text: ABSTRACT: Some new trans-dihydronarciclasine derivatives containing a 1,4-benzodioxane moiety were stereoselectively synthesised using our feasible and efficient method developed recently. These new phenanthridone alkaloid analogues were obtained in both racemic and optically active forms. High enantioselectivities (up to 99% ee) were achieved by applying (8S,9S)-9-amino(9-deoxy)epiquinine as an organocatalyst. Due to a side reaction, various methoxyphenanthridine regioisomers were also prepared which afforded further synthetic trans-dihydronarciclasine analogues modified in the ring A of the phenanthridone scaffold. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00706-018-2287-7) contains supplementary material, which is available to authorized users.


title: Evolution and Variation of the SARS-CoV Genome

text: Knowledge of the evolution of pathogens is of great medical and biological significance to the prevention, diagnosis, and therapy of infectious diseases. In order to understand the origin and evolution of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus), we collected complete genome sequences of all viruses available in GenBank, and made comparative analyses with the SARS-CoV. Genomic signature analysis demonstrates that the coronaviruses all take the TGTT as their richest tetranucleotide except the SARS-CoV. A detailed analysis of the forty-two complete SARS-CoV genome sequences revealed the existence of two distinct genotypes, and showed that these isolates could be classified into four groups. Our manual analysis of the BLASTN results demonstrates that the HE (hemagglutinin-esterase) gene exists in the SARS-CoV, and many mutations made it unfamiliar to us.


title: A molecular modeling approach to identify effective antiviral phytochemicals against the main protease of SARS-CoV-2

text: The main protease of SARS-CoV-2 is one of the important targets to design and develop antiviral drugs. In this study, we have selected 40 antiviral phytochemicals to find out the best candidates which can act as potent inhibitors against the main protease. Molecular docking is performed using AutoDock Vina and GOLD suite to determine the binding affinities and interactions between the phytochemicals and the main protease. The selected candidates strongly interact with the key Cys145 and His41 residues. To validate the docking interactions, 100 ns molecular dynamics (MD) simulations on the five top-ranked inhibitors including hypericin, cyanidin 3-glucoside, baicalin, glabridin, and α-ketoamide-11r are performed. Principal component analysis (PCA) on the MD simulation discloses that baicalin, cyanidin 3-glucoside, and α-ketoamide-11r have structural similarity with the apo-form of the main protease. These findings are also strongly supported by root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), and solvent accessible surface area (SASA) investigations. PCA is also used to find out the quantitative structure-activity relationship (QSAR) for pattern recognition of the best ligands. Multiple linear regression (MLR) of QSAR reveals the R(2) value of 0.842 for the training set and 0.753 for the test set. Our proposed MLR model can predict the favorable binding energy compared with the binding energy detected from molecular docking. ADMET analysis demonstrates that these candidates appear to be safer inhibitors. Our comprehensive computational and statistical analysis show that these selected phytochemicals can be used as potential inhibitors against the SARS-CoV-2. Communicated by Ramaswamy H. Sarma


title: Different Lineage of Porcine Deltacoronavirus in Thailand, Vietnam and Lao PDR in 2015

text: Porcine deltacoronavirus (PDCoV) was detected by RT‐PCR in 12 of 97 (12.4%) intestinal samples collected during 2015 from piglets with diarrhoea in Thailand, Vietnam and Lao PDR. Spike, membrane and nucleocapsid genes were characterized, and phylogenetic analyses demonstrated that PDCoV isolates from Thai and Lao PDR form a novel cluster, separated from US and China isolates, but relatively were more closely related to China PDCoV than US isolates. Vietnam PDCoVs, however, were grouped together with US PDCoV. The analyses of amino acid changes suggested that they were from different lineage.


Anwendung von Biologika bei allergischen und Typ-2-entzündlichen Erkrankungen in der aktuellen Covid-19-Pandemie(a, b, c): Positionspapier des Ärzteverbands Deutscher Allergologen (AeDA)A, der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI)B, der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)C, der Österreichischen Gesellschaft für Allergologie und Immunologie (ÖGAI)D, der Luxemburgischen Gesellschaft für Allergologie und Immunologie (LGAI)E, der Österreichischen Gesellschaft für Pneumologie (ÖGP)F in Kooperation mit der deutschen, österreichischen, und schweizerischen ARIA-GruppeG und der Europäischen Akademie für Allergologie und Klinische Immunologie (EAACI)H


title: Amid conference cancellations, leaders advance with support

text: In the wake of the COVID‐19 pandemic and in the interest of keeping staff, employees and consumers with mental health and substance use disorders safe, many organizations have had to cancel scheduled conferences and annual meetings. Officials and leaders, meanwhile, are moving forward with helping their members and the public stay safe during this outbreak.


title: Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator

text: BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.


docid: wlwxwrer

title: Interleukin‐18: Biological properties and role in disease pathogenesis

text: Initially described as an interferon (IFN)γ‐inducing factor, interleukin (IL)‐18 is indeed involved in Th1 and NK cell activation, but also in Th2, IL‐17‐producing γδ T cells and macrophage activation. IL‐18, a member of the IL‐1 family, is similar to IL‐1β for being processed by caspase 1 to an 18 kDa‐biologically active mature form. IL‐18 binds to its specific receptor (IL‐18Rα, also known as IL‐1R7) forming a low affinity ligand chain. This is followed by recruitment of the IL‐18Rβ chain. IL‐18 then uses the same signaling pathway as IL‐1 to activate NF‐kB and induce inflammatory mediators such as adhesion molecules, chemokines and Fas ligand. IL‐18 also binds to the circulating high affinity IL‐18 binding protein (BP), such as only unbound free IL‐18 is active. IL‐18Rα may also bind IL‐37, another member of the IL‐1 family, but in association with the negative signaling chain termed IL‐1R8, which transduces an anti‐inflammatory signal. IL‐18BP also binds IL‐37 and this acts as a sink for the anti‐inflammatory properties of IL‐37. There is now ample evidence for a role of IL‐18 in various infectious, metabolic or inflammatory diseases such as influenza virus infection, atheroma, myocardial infarction, chronic obstructive pulmonary disease, or Crohn's disease. However, IL‐18 plays a very specific role in the pathogenesis of hemophagocytic syndromes (HS) also termed Macrophage Activation Syndrome. In children affected by NLRC4 gain‐of‐function mutations, IL‐18 circulates in the range of tens of nanograms/mL. HS is treated with the IL‐1 Receptor antagonist (anakinra) but also specifically with IL‐18BP. Systemic juvenile idiopathic arthritis or adult‐onset Still's disease are also characterized by high serum IL‐18 concentrations and are treated by IL‐18BP.


title: Persistence of Viruses in Upper Respiratory Tract of Children with Asthma

text: Abstract Objectives: Nasopharyngeal swabs of 50 asthmatic children in the symptom-free period were examined for the presence of adenoviruses, rhinoviruses and coronaviruses. A control group of 20 healthy individuals was included in this study. Methods: A polymerase chain reaction was used to detect adenovirus DNA and rhinovirus and coronavirus complementary DNA. The fragments of amplified genetic material were visualized with the use of agarose gel electrophoresis. Results: Adenovirus DNA was found in 78.4% of asthmatic children, rhinovirus RNA in 32.4% and coronavirus RNA in 2.7%. Adenovirus DNA was detected in one of the 20 nasopharyngeal swabs of healthy controls; the rest of the control samples were negative. Conclusions: The persistent presence of viruses in the upper respiratory tract of asthmatic children shows a possible connection between viral infections and asthma.


Lessons learnt from the human infections of avian-origin influenza A H7N9 virus: Live free markets and human health


title: Major Infection Events Over 5 Years: How Is Media Coverage Influencing Online Information Needs of Health Care Professionals and the Public?

text: BACKGROUND: The last decade witnessed turbulent events in public health. Emerging infections, increase of antimicrobial resistance, deliberately released threats and ongoing battles with common illnesses were amplified by the spread of disease through increased international travel. The Internet has dramatically changed the availability of information about outbreaks; however, little research has been done in comparing the online behavior of public and professionals around the same events and the effect of media coverage of outbreaks on information needs. OBJECTIVE: To investigate professional and public online information needs around major infection outbreaks and correlate these with media coverage. Questions include (1) How do health care professionals’ online needs for public health and infection control information differ from those of the public?, (2) Does dramatic media coverage of outbreaks contribute to the information needs among the public?, and (3) How do incidents of diseases and major policy events relate to the information needs of professionals? METHODS: We used three longitudinal time-based datasets from mid-2006 until end of 2010: (1) a unique record of professional online behavior on UK infection portals: National electronic Library of Infection and National Resource of Infection Control (NeLI/NRIC), (2) equivalent public online information needs (Google Trends), and (3) relevant media coverage (LexisNexis). Analysis of NeLI/NRIC logs identified the highest interest around six major infectious diseases: Clostridium difficile (C difficile)/Methicillin-resistant Staphylococcus aureus (MRSA), tuberculosis, meningitis, norovirus, and influenza. After pre-processing, the datasets were analyzed and triangulated with each other. RESULTS: Public information needs were more static, following the actual disease occurrence less than those of professionals, whose needs increase with public health events (eg, MRSA/C difficile) and the release of major national policies or important documents. Media coverage of events resulted in major public interest (eg, the 2007/2008 UK outbreak of C difficile/MRSA). An exception was norovirus, showing a seasonal pattern for both public and professionals, which matched the periodic disease occurrence. Meningitis was a clear example of a disease with heightened media coverage tending to focus on individual and celebrity cases. Influenza was a major concern during the 2009 H1N1 outbreak creating massive public interest in line with the spring and autumn peaks in cases; although in autumn 2009, there was no corresponding increase in media coverage. Online resources play an increasing role in fulfilling professionals’ and public information needs. CONCLUSIONS: Significant factors related to a surge of professional interest around a disease were typically key publications and major policy changes. Public interests seem more static and correlate with media influence but to a lesser extent than expected. The only exception was norovirus, exhibiting online public and professional interest correlating with seasonal occurrences of the disease. Public health agencies with responsibility for risk communication of public health events, in particular during outbreaks and emergencies, need to collaborate with media in order to ensure the coverage is high quality and evidence-based, while professionals’ information needs remain mainly fulfilled by online open access to key resources.


Probiotics and COVID-19 – Authors' reply


title: Molecular cloning, expression, purification and crystallographic analysis of PRRSV 3CL protease

text: 3CL protease, a viral chymotrypsin-like proteolytic enzyme, plays a pivotal role in the transcription and replication machinery of many RNA viruses, including porcine reproductive and respiratory syndrome virus (PRRSV). In this study, the full-length 3CL protease from PRRSV was cloned and overexpressed in Escherichia coli. Crystallization experiments yielded crystals that diffracted to 2.1 Å resolution and belong to space group C2, with unit-cell parameters a = 112.31, b = 48.34, c = 42.88 Å, β = 109.83°. The Matthews coefficient and the solvent content were calculated to be 2.49 Å(3) Da(−1) and 50.61%, respectively, for one molecule in the asymmetric unit.


Dental and medical collaboration during COVID‐19


title: Performance of pigs kept under different sanitary conditions affected by protein intake and amino acid supplementation(,)(2)

text: There is growing evidence that requirements for particular AA increase when pigs are kept under low sanitary conditions. The extent to which reduction in growth performance is related to these increased requirements is unclear. To evaluate this relationship, an experiment (2 × 2 × 2 factorial arrangement) was performed with 612 male pigs (9 per pen) kept under low sanitary conditions (LSC) or high sanitary conditions (HSC) and offered ad libitum access to either a normal CP concentration diet (NP; 17, 15, and 15% CP for the starter, grower, and finisher phase, respectively) or a low CP concentration diet (LP; 20% CP reduced relative to NP for each phase), each of which containing a basal AA profile (AA-B) or a supplemented AA profile (AA-S). The supplemented diet type contained 20% more Met, Thr, and Trp relative to Lys on an apparent ileal digestible basis compared with the basal diet type. Pigs were followed for a complete fattening period and slaughtered at a targeted pen weight of 110 kg. Haptoglobin concentrations in serum (0.92 g/L for LSC and 0.78 g/L for HSC) and IgG antibody titers against keyhole limpet hemocyanin (3.53 for LSC and 3.08 for HSC) collected in the starter, grower, and finisher phases and pleuritis scores at slaughter (0.51 for LSC and 0.20 for HSC) were greater for LSC pigs compared with HSC pigs (P ≤ 0.01), illustrating that sanitary conditions affected health conditions. The ADG and G:F were greater for HSC pigs compared with LSC pigs (P ≤ 0.01). The number of white blood cells (WBC) was higher in (AA-S)–fed pigs compared with (AA-B)–fed pigs when kept at LSC but not at HSC [SS (sanitary conditions) × AA interaction, P = 0.04]. Pigs fed NP had a lower number of WBC compared with pigs fed LP (P = 0.02). The number of platelets in pigs fed AA-S diets was higher compared with pigs fed AA-B diets (P ≤ 0.01). A 20% reduction in dietary supplementation of Met, Thr, and Trp relative to Lys decreased G:F more in LSC pigs than in HSC pigs (interaction, P = 0.03), illustrating that dietary requirements for these AA differ depending on sanitary conditions. This study, performed under practical conditions, shows that AA requirements are dependent on sanitary conditions. Furthermore, supplementation of diets with particular AA may improve performance, especially under poor hygienic conditions. Dietary protein concentration as well as Met, Thr, and Trp supplementation can modify immune status, which may influence resistance to subclinical and clinical diseases.


title: Etiology and Incidence of Viral and Bacterial Acute Respiratory Illness among Older Children and Adults in Rural Western Kenya, 2007–2010

text: BACKGROUND: Few comprehensive data exist on disease incidence for specific etiologies of acute respiratory illness (ARI) in older children and adults in Africa. METHODOLOGY/PRINCIPAL FINDINGS: From March 1, 2007, to February 28, 2010, among a surveillance population of 21,420 persons >5 years old in rural western Kenya, we collected blood for culture and malaria smears, nasopharyngeal and oropharyngeal swabs for quantitative real-time PCR for ten viruses and three atypical bacteria, and urine for pneumococcal antigen testing on outpatients and inpatients meeting a ARI case definition (cough or difficulty breathing or chest pain and temperature >38.0°C or oxygen saturation <90% or hospitalization). We also collected swabs from asymptomatic controls, from which we calculated pathogen-attributable fractions, adjusting for age, season, and HIV-status, in logistic regression. We calculated incidence by pathogen, adjusting for health-seeking for ARI and pathogen-attributable fractions. Among 3,406 ARI patients >5 years old (adjusted annual incidence 12.0 per 100 person-years), influenza A virus was the most common virus (22% overall; 11% inpatients, 27% outpatients) and Streptococcus pneumoniae was the most common bacteria (16% overall; 23% inpatients, 14% outpatients), yielding annual incidences of 2.6 and 1.7 episodes per 100 person-years, respectively. Influenza A virus, influenza B virus, respiratory syncytial virus (RSV) and human metapneumovirus were more prevalent in swabs among cases (22%, 6%, 8% and 5%, respectively) than controls. Adenovirus, parainfluenza viruses, rhinovirus/enterovirus, parechovirus, and Mycoplasma pneumoniae were not more prevalent among cases than controls. Pneumococcus and non-typhi Salmonella were more prevalent among HIV-infected adults, but prevalence of viruses was similar among HIV-infected and HIV-negative individuals. ARI incidence was highest during peak malaria season. CONCLUSIONS/SIGNFICANCE: Vaccination against influenza and pneumococcus (by potential herd immunity from childhood vaccination or of HIV-infected adults) might prevent much of the substantial ARI incidence among persons >5 years old in similar rural African settings.


title: Incidence of Circulating Antibodies Against Hemagglutinin of Influenza Viruses in the Epidemic Season 2013/2014 in Poland

text: The aim of this study was to determine the level of antibodies against hemagglutinin of influenza viruses in the sera of people in different age groups in the epidemic season 2013/2014 in Poland. The level of anti-hemagglutinin antibodies was determined by hemagglutination inhibition test (HAI). A total number of 1,050 randomly selected sera was tested in seven age groups. The level of antibodies against influenza viruses was very low, which indicates that the people have not been vaccinated against influenza in the epidemic season 2013/2014. The value of protection rate against influenza in the Polish population is very low. These results are worrying, because complications of influenza may be harmful to health and even life-threatening to persons who are not vaccinated. Furthermore, these results confirm the circulation of three antigenically different influenza virus strains, two subtypes of influenza A virus – A/California/7/2009/(H1N1)pdm09 and A/Victoria/361/2011(H3N2) - and B/Massachusetts/2/2012.


title: Association of targeted multiplex PCR with resequencing microarray for the detection of multiple respiratory pathogens

text: A large number of viral and bacterial organisms are responsible for community-acquired pneumonia (CAP) which contributes to substantial burden on health management. A new resequencing microarray (RPM-IVDC1) associated with targeted multiplex PCR was recently developed and validated for multiple respiratory viruses detection and discrimination. In this study, we evaluated the capability of RPM-IVDC1 for simultaneous identification of multiple viral and bacterial organisms. The nasopharyngeal aspirates (NPAs) of 110 consecutive CAP patients, aged from 1 month to 96 years old, were collected from five distinct general hospitals in Beijing during 1-year period. The samples were subjected to the RPM-IVDC1 established protocol as compared to a real-time PCR (qRT-PCR), which was used as standard. The results of virus detection were consistent with those previously described. A total of 37 of Streptococcus pneumoniae, 14 of Haemophilus influenzae, 10 of Mycoplasma pneumoniae, two of Klebsiella pneumoniae and one of Moraxella catarrhalis were detected by RPM-IVDC1. The sensitivities and specificities were compared with those of qRT-PCR for S. pneumoniae (100, 100%, respectively), H. influenzae (92.3, 97.9%, respectively), M. pneumoniae (69.2, 99.0%, respectively), K. pneumoniae (100, 100%, respectively), and M. catarrhalis (100, 100%, respectively). Additional 22 of Streptococcus spp., 24 of Haemophilus spp. and 16 of Neisseria spp. were identified. In addition, methicillin-resistant and carbapenemases allele were also found in nine of Staphylococcus spp. and one of K. pneumoniae, respectively. These results demonstrated the capability of RPM-IVDC1 for simultaneous detection of broad-spectrum respiratory pathogens in complex backgrounds and the advantage of accessing to the actual sequences, showing great potential use of epidemic outbreak investigation. The detection results should be carefully interpreted when introducing this technique in the clinical diagnostics.


title: Chapter 8 In vivo experimental models of infection and disease

text: Abstract Human and animal models continue to play a crucial role in research to understand host immunity to rhinovirus (RV) and identify disease mechanisms. Human models have provided direct evidence that RV infection is capable of exacerbating chronic respiratory diseases and identified immunological processes that correlate with clinical disease outcomes. Mice are the most commonly used nonhuman experimental RV infection model. Although semipermissive, under defined experimental conditions sufficient replication occurs to induce host immune responses that recapitulate immunity and disease during human infection. The capacity to use genetically modified mouse strains and drug interventions has shown the mouse model to be an invaluable research tool defining causal relationships between host immunity and disease and supporting development of new treatments. Used in combination the insights achieved from human and animal experimental infection models provide complementary insights into RV biology and yield novel therapeutic options to reduce the burden of RV-induced disease.


title: Disruption of joint arthroplasty services in Europe during the COVID-19 pandemic: an online survey within the European Hip Society (EHS) and the European Knee Associates (EKA)

text: PURPOSE: The aim of the present study was to evaluate the impact of the coronavirus (COVID-19) pandemic on joint arthroplasty service in Europe by conducting an online survey of arthroplasty surgeons. METHODS: The survey was conducted in the European Hip Society (EHS) and the European Knee Associates (EKA). The survey consisted of 20 questions (single, multiple choice, ranked). Four topics were addressed: (1) origin and surgical experience of the participant (four questions); (2) potential disruption of arthroplasty surgeries (12 questions); (3) influence of the COVID-19 pandemic on the particular arthroplasty surgeon (four questions); (4) a matrix provided 14 different arthroplasty surgeries and the participant was asked to state whether dedicated surgery was stopped, delayed or cancelled. RESULTS: Two-hundred and seventy-two surgeons (217 EHS, 55 EKA) from 40 different countries participated. Of the respondents, 25.7% stated that all surgeries were cancelled in their departments, while 68.4% responded that elective inpatient procedures were no longer being performed. With regard to the specific surgical procedures, nearly all primary TJA were cancelled (92.6%) as well as aseptic revisions (94.7%). In most hospitals, periprosthetic fractures (87.2%), hip arthroplasty for femoral neck fractures and septic revisions for acute infections (75.8%) were still being performed. CONCLUSION: During the current 2020 COVID-19 pandemic, we are experiencing a near-total shutdown of TJA. A massive cutback was observed for primary TJA and revision TJA, even in massively failed TJA with collapse, dislocation, component failure or imminent dislocation. Only life-threatening pathologies like periprosthetic fractures and acute septic TJA are currently undergoing surgical treatment. LEVEL OF EVIDENCE: V. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00167-020-06033-1) contains supplementary material, which is available to authorized users.


title: Procédure de dépistage d’une infection à COVID-19 en milieu de travail structuré africain

text: Résumé Alors qu’il n’existe de recommandation spécifique en Afrique Subsaharienne, le but de ce travail est de proposer aux professionnels de santé, un outil simple de détection des cas de COVID-19 parmi les travailleurs du secteur formel dans cette région. En effet la riposte contre l’infection à COVID-19 en milieu de travail formel africain doit pouvoir s’insérer dans le dispositif national et comprendre : l’installation au niveau de chaque entreprise d’une cellule de gestion de la riposte bien articulée avec le comité d’hygiène et de sécurité du travail ; la sensibilisation et formation des partenaires sociaux sur les aspects liés à la connaissanceet les moyens de prévention de l’infection ; la mise en route d’une procédure de dépistage et d’un circuit pour les cas détectés ; l’évaluation et le suivi de l’impact psychosocial et économique de l’infection. Summary Though there is no specific guidelines in Sub-Saharan Africa, the aim is to suggest to health practitioners, a simple screening tool of COVID-19 cases in the formal workforce in the region. Indeed the COVID-19 response in the formal African workplace should clearly be integrated into the national system and should include: the setting up, in each company, of a response management unit that works in collaboration with the occupational health and safety committee; awareness-raising and training of social partners on aspects relating to knowledge of the disease and prevention measures; implementation of a procedure for screening and handling cases detected; evaluation and monitoring of the psychosocial and economic impact of the disease.


title: Examining the relationship between infectious diseases and flooding in Europe: A systematic literature review and summary of possible public health interventions

text: Introduction Many infectious diseases are sensitive to climatic changes; specifically, flooding. This systematic literature review aimed to strengthen the quality and completeness of evidence on infectious diseases following flooding, relevant to Europe. Methods A systematic literature review from 2004–2012 was performed. Focused searches of the following databases were conducted: Medline, Scopus, PubMed, Cochrane Library, and Evidence Aid. Personal communications with key informants were also reviewed. Results Thirty-eight studies met the inclusion criteria. Evidence suggested that water-borne, rodent-borne, and vector-borne diseases have been associated with flooding in Europe, although at a lower incidence than developing countries. Conclusion Disease surveillance and early warning systems, coupled with effective prevention and response capabilities, can reduce current and future vulnerability to infectious diseases following flooding.


Molecular epidemiology of circulating human coronaviruses in children at a tertiary hospital in Catalonia (Spain) from 2014 to 2016


title: IL‐4 induces a suppressive IL‐10‐producing CD8(+) T cell population via a Cdkn2a‐dependent mechanism

text: CD8(+) T cells play an important role in immune regulation and effective immune responses against tumor cells, viral infection, and intracellular pathogens. In this report, using tiger or 10BiT mice, we defined a population of IL‐10‐producing CD8(+) T cells that were induced by IL‐4. These IL‐10(+)CD8(+) T cells possessed a strong inhibitory effect on the CD4(+) T cell proliferation in an IL‐10‐dependent and cell contact‐dependent fashion. In comparison with IL‐10(−)CD8(+) T cells, IL‐10(+)CD8(+) T cells expressed an array of Th2‐like cytokines (IL‐4, IL‐5), perforin, and granzymes, as well as the cell cycle regulatory protein Cdkn2a. Interestingly, knockdown of cdkn2a using siRNA reduced IL‐4‐induced IL‐10 production significantly. Furthermore, CD8(+) T cells from Cdkn2a(−/−) mice produced a significantly lower amount of IL‐10, and the effect was limited to CD8(+) T cells but not observed in CD4(+) T cells and APCs. Finally, IL‐10(+)CD8(+) T cells played a protective role in the TNBS‐induced murine colitis model, indicating a critical role of this population of CD8(+) T cells in regulatory immune responses. Taken together, we have defined a population of IL‐10‐producing CD8(+) Tregs induced by IL‐4 and mediated by Cdkn2a.


title: Humoral innate immune response and disease

text: The humoral innate immune response consists of multiple components, including the naturally occurring antibodies (NAb), pentraxins and the complement and contact cascades. As soluble, plasma components, these innate proteins provide key elements in the prevention and control of disease. However, pathogens and cells with altered self proteins utilize multiple humoral components to evade destruction and promote pathogy. Many studies have examined the relationship between humoral immunity and autoimmune disorders. This review focuses on the interactions between the humoral components and their role in promoting the pathogenesis of bacterial and viral infections and chronic diseases such as atherosclerosis and cancer. Understanding the beneficial and detrimental aspects of the individual components and the interactions between proteins which regulate the innate and adaptive response will provide therapeutic targets for subsequent studies.


An Open Question: Is It Rational to Inhibit the mTor-Dependent Pathway as COVID-19 Therapy?


title: Pour une prise en charge préventive de la maladie d’Alzheimer

text: Résumé Les démences et la maladie d’Alzheimer (MA), en particulier, vont devenir de plus en plus un enjeu de santé publique. Trois données importantes peuvent cependant modifier le poids de ces pathologies : (1) de simples mesures d’hygiène de vie (contrôle de facteurs de risque vasculaire, activité physique et stimulation cognitive) instaurées chez les jeunes adultes ont un impact sur un déclin cognitif ultérieur ; (2) chez des sujets âgés à risque, ces mêmes dispositions retardent l’entrée dans la maladie et (3) enfin et pour la première fois, un anticorps anti-amyloïde aurait montré un effet significatif sur l’évolution de la MA chez des patients au stade débutant. Il ressort de ces travaux qu’il faut se préparer à reconsidérer la stratégie de prise en charge des troubles cognitifs, qu’ils soient mineurs ou majeurs, et de la MA en particulier. L’entrée des patients dans le parcours de soins reste aujourd’hui trop tardive. La solution est d’agir plus précocement, voire de façon préventive. Il faut développer une offre de soins adaptée à cette situation nouvelle afin d’agir sur la maladie le plus tôt possible, fondée sur : des algorithmes prédictifs pour déterminer chez les sujets sans symptômes spécifiques ceux qui seront à risque de développer une pathologie dégénérative. Ces algorithmes devront être mis au point à partir de données démographiques, familiales, cognitives, génomiques et biologiques, comme celles recueillies dans le projet « Santé-Cerveau » développé en partenariat avec l’ARS et les médecins généralistes ; le renforcement des activités de prévention dans les 450 centres mémoire de proximité disponibles en France et les 26 CM2R et la transformation de quelques-uns de ces centres experts en cliniques de prévention de la démence pour tester les mesures de prévention, initier des programmes d’éducation thérapeutique multidomaine et les valider, communiquer sur le risque, répondre à la demande de sujets inquiets et déterminer, chez ceux-ci, à l’aide des algorithmes, le niveau de risque qu’ils ont de déclarer une MA dans les mois et années qui viennent, en tenant compte de la compétition entre les risques. On peut ainsi se préparer à faire bénéficier précocement les uns et les autres des traitements pharmacologiques susceptibles d’exister. Summary Dementias, and Alzheimer's disease (AD) in particular, will increasingly become a public health issue. However, three major data may change the severity of these pathologies: in young adults, simple measures of healthy lifestyle (control of vascular risk factors, physical activity and cognitive stimulation), have an impact on a future cognitive decline; the same lifestyle interventions may delay the start of the disease for elderly people potentially at-risk; finally, and for the first time, a monoclonal antibody directed against amyloid lesions has just shown a significant effect on the progression of AD in patients at an early stage of the disease. According to these results, we will have to reconsider the strategy for managing minor or severe cognitive disorders and particularly AD. Nowadays, patients start the care process too late. The solution is to act earlier, even preventively. It is necessary to improve a care offer adapted to this new situation in order to impact on the disease as soon as possible, even before the onset of symptoms, based on: predictive algorithms aimed at establishing whose cognitively unimpaired individuals may further develop the disease. These algorithms will be based on demographic, family, cognitive, genomic and biological data, such as in the “Santé Cerveau” project developed in partnership with the Health Regional Agency (ARS) and the general practitioners and some expert centers must become “dementia prevention clinics” to test prevention measures, initiate and validate multi-domain therapeutic education programs, to disclose about the risk in response to the request of worried patients, and to propose early pharmacological treatments if these individuals are on the way to declare AD in the coming months, taking into account competition between risks. This will allow to prepare to make use of new pharmacological treatments that might be discovered.


title: Small business loan eligibility promising for nonprofits

text: Nonprofit organizations receiving Medicaid payments are encouraged that they are now eligible for small business loans courtesy of the $2 trillion COVID‐19 relief package (see story, beginning on page 1). Just a few short weeks ago, in an earlier version of the legislation, mental health providers with Medicaid‐participating business were excluded from being eligible for these important loans.


title: Serum LD1 isoenzyme and blood lymphocyte subsets as prognostic indicators for severe acute respiratory syndrome

text: Background. The pathophysiology of severe acute respiratory syndrome (SARS) is at present poorly understood, but advanced age and serum total lactate dehydrogenase (LD) activity >300 U L(−1) have been associated with adverse clinical outcomes. Blood leucocytes and lymphocyte subsets were reported to decrease, respectively, in 47% and up to 100% of 38 patients in Beijing. However, their prognostic implications have not been thoroughly investigated. Objective. To investigate serum total LD, LD isoenzymes, and other parameters including blood lymphocyte subsets as prognostic indicators in SARS patients for adverse clinical outcomes in terms of admission to intensive care unit (ICU) and death. Design. Retrospective analysis. Subjects and methods. A total of 109 patients with a clinical diagnosis of SARS according to the modified World Health Organization case definition of SARS were recruited from two major acute hospitals in Hong Kong. They were either involved in the initial outbreak of SARS, or cases from the community outbreak of Amoy Gardens between 10 March and 5 May 2003. The clinical diagnosis was subsequently confirmed by serological test and/or molecular analysis. Serum total LD and LD isoenzyme activities, complete blood picture with total leucocyte count and differential counts, absolute counts of CD3+, CD4+, CD8+, natural killer cells and B lymphocytes were measured daily upon admission. Receiver operating characteristic curve analysis was used to determine and compare different cut‐offs for various biochemical and immunological parameters at peak serum total LD concentration in predicting adverse clinical outcomes. Results. Of a total of 109 patients, 41 were admitted to ICU and 42 died. Of 42 fatal patients, 24 died in ICU and 18 died in general medical wards. Age was found to be an independent prognostic indictor for death with an area under curve (AUC) of 0.96 [95% confidence interval (CI) = 0.90–0.99] but not for admission to ICU [AUC = 0.61 (CI = 0.51–0.70)]. Whilst serum total LD could only achieve AUC of 0.68 (CI = 0.59–0.77) for predicting death, LD1 isoenzyme was found to be the best biochemical prognostic indicator with AUC of 0.84 (CI = 0.75–0.90), sensitivity of 62% (CI = 46–76%), specificity of 93% (CI = 83–98%) at cut‐off activity of ≥80 U L(−1). CD3+, CD4+, CD8+ and natural killer cell counts were promising immunological prognostic indicators for predicting admission to ICU with AUC of 0.94 (CI = 0.86–0.98), 0.91 (CI = 0.81–0.96), 0.93 (CI = 0.85–0.98), and 0.87 (CI = 0.76–0.94), respectively. Conclusions. Apart from age, serum LD1 activity was the best prognostic indicator for predicting death in patients with SARS compared with serum total LD activity, haemoglobin concentration, leucocyte and lymphocyte counts. Its release could possibly be from blood erythrocytes and body tissues other than the myocardium. Blood CD3+, CD4+, CD8+ and natural killer cell counts were found to be good prognostic indicators for predicting admission to ICU in patients with SARS compared with age, leucocyte count and LD isoenzymes. The suppressed CD3+, CD4+, CD8+, and natural killer cell counts were also implicated in the pathophysiology of SARS. Patients with increased serum LD1 should be closely monitored to ensure prompt management, and preparation for admission to ICU could be planned ahead for patients with suppressed lymphocyte subsets.


COVID-19 cancer conundrum—evidence driving decisions or the lack of it?


title: Macrophage Coordination of the Interferon Lambda Immune Response

text: Lambda interferons (IFN-λs) are a major component of the innate immune defense to viruses, bacteria, and fungi. In human liver, IFN-λ not only drives antiviral responses, but also promotes inflammation and fibrosis in viral and non-viral diseases. Here we demonstrate that macrophages are primary responders to IFN-λ, uniquely positioned to bridge the gap between IFN-λ producing cells and lymphocyte populations that are not intrinsically responsive to IFN-λ. While CD14(+) monocytes do not express the IFN-λ receptor, IFNLR1, sensitivity is quickly gained upon differentiation to macrophages in vitro. IFN-λ stimulates macrophage cytotoxicity and phagocytosis as well as the secretion of pro-inflammatory cytokines and interferon stimulated genes that mediate immune cell chemotaxis and effector functions. In particular, IFN-λ induced CCR5 and CXCR3 chemokines, stimulating T and NK cell migration, as well as subsequent NK cell cytotoxicity. Using immunofluorescence and cell sorting techniques, we confirmed that human liver macrophages expressing CD14 and CD68 are highly responsive to IFN-λ ex vivo. Together, these data highlight a novel role for macrophages in shaping IFN-λ dependent immune responses both directly through pro-inflammatory activity and indirectly by recruiting and activating IFN-λ unresponsive lymphocytes.


title: Evolutionary rate shifts suggest species-specific adaptation events in HIV-1 and SIV

text: The process of molecular adaptation following a cross-species virus transmission event is currently poorly understood. Here, we identified 137 protein sites that experienced deceleration in their rate of evolution along the HIV-1/SIV phylogeny, likely indicating gain-of-function and consequent adaptation. The majority of such events occurred in parallel to cross-species transmission events and varied between HIV-1 groups, indicating independent adaptation strategies. The evolutionary rate decelerations we found were particularly prominent in accessory proteins that counteract host antiviral restriction factors, suggesting that these factors are a major barrier to viral adaptation to a new host. Surprisingly, we observed that the non-pandemic HIV-1 group O, derived from gorillas, exhibited more rate deceleration events than the pandemic group M, derived from chimpanzees. We suggest that the species barrier is higher when the genetic distance of the hosts increases. Our approach paves the way for subsequent studies on cross-species transfers in other major pathogens.


title: Early loss of astrocytes in herpes simplex virus–induced central nervous system demyelination

text: Immunohistochemistry was used to study herpes simplex virus type 1–induced central nervous system demyelination in the trigminal root entry zone of mice inoculated with herpes simplex virus type 1 by the corneal route. There was no change in peripheral nervous system myelin as shown by immunostaining for Po glycoprotein. Double immunoperoxidase staining for herpes simplex virus type 1 antigens and glial fibrillary acidic protein showed that most of the infected cells were astrocytes. Glial fibrillary acidic protein immunostaining was completely lost in the inferior medial portion of the trigeminal root entry zone at 6 days after herpes simplex virus type 1 inoculation, a time when central nervous system myelin was preserved as indicated by immunostaining for myelin basic protein. The pattern of glial fibrillary acidic protein staining did not change and herpes simplex virus type 1 antigens were no longer detected after day 8. There was a progressive loss of myelin basic protein staining within the area unstained by glial fibrillary acidic protein antisera on days 8 to 14. This pattern of astrocyte loss before central nervous system demyelination is strikingly different from the reactive astrocytosis seen in other demyelinating lesions, such as acute experimental allergic encephalomyelitis, progressive multifocal leukoencephalopathy, or acute multiple sclerosis. Herpes simplex virus type 1 infection in mice provides an unusual model of acute central nervous system demyelination preceded by a loss of astrocytes.


The role of viruses in the aetiology of IRA in Peruvian children