docid: azamwuzl

title: The changing face of family medicine in the covid and post‐covid era

text: In the last decade, family doctors (FD), mainly devoted to the management of elderly and multi‐morbid people, have become increasingly involved in managing patients under innovative therapy and by dealing with electronic health record systems providing faster connection with patients and other health workers.


docid: xnillpzd

title: Helper virus-independent trans-replication of hepatitis C virus-derived minigenome

text: Abstract We have previously described a synthetic T7-driven cDNA minigenome containing the antisense sequence of luciferase gene and internal ribosome entry site of encephalomyocarditis virus flanked by 5′- and 3′-end sequences of hepatitis C virus (HCV) that contain cis-acting replication elements. Synthesis of minus-strand RNA from the artificial minigenome was determined by using Huh-7 cells harboring autonomously replicating HCV subgenome as a helper for provision of functional replication components. To further confirm and extend these studies, we investigated here whether the minigenome replication system could be reconstituted by transfection of naïve Huh-7 cells with plasmid expressing nonstructural (NS) proteins. Reporter assay and Northern blot analysis revealed that trans-expression of NS proteins from 3 to 5 resulted in high level of luciferase activity and synthesized minus-strand RNA. The analogous result was also obtained with the minigenome derived from HCV 2a, and both HCV 1b- and 2a-derived NS protein were able to support the chimeric minigenomes whose 5′- or 3′-end was replaced by the respective region of the heterologous virus. These results provide a basis for establishing the reverse genetic system that is helpful to study cis- and trans-acting factors involved in HCV RNA replication.


title: Spectrum of Neuropsychiatric Manifestations in COVID-19

text: Corona Virus Disease 2019 (COVID-19) emerged in December 2019 from Wuhan, China. It typically presents with mild upper respiratory tract infection symptoms and may have life threatening complications, including acute respiratory distress syndrome, acute stroke, myocardial infarction, kidney failure, shock, and even death. Coronavirus infections are known to have neuroinvasive potential with consequent neuropsychiatric manifestations. We analyzed COVID-19 adult patients in the TriNetX database, which is a global health collaborative clinical research platform collecting real-time electronic medical records data from a network of health care organizations (HCOs) from January 20, 2020 to June 10(th), 2020. 40,469 patients were diagnosed with COVID-19 among whom 9086 (22.5%) patients had neuropsychiatric manifestations. The most common neurologic manifestations included headache (3.7%) and sleep disorders (3.4%), Encephalopathy (2.3%), Stroke and transient ischemic attack (TIA) (1.0%) and 0.6% had seizures. Most common psychiatric manifestations included anxiety and other related disorders (4.6%), mood disorders (3.8%), while 0.2% patients had suicidal ideation. Early recognition and prompt management of neuropsychiatric manifestations in these patients have a potential to decrease overall morbidity and mortality.


Advances in Transfusion Medicine


title: In vitro and in vivo studies of the Interferon-alpha action on distinct Orthobunyavirus

text: Abstract Oropouche, Caraparu, Guama, Guaroa and Tacaiuma viruses (Orthobunyavirus genus) cause human febrile illnesses and/or encephalitis. To achieve a therapeutical agent to prevent and/or treat these diseases we evaluated the antiviral action of Interferon-alpha (IFN-α) on these orthobunyaviruses. In vitro results showed that all the studied orthobunyaviruses are susceptible to antiviral action of IFN-α, but this susceptibility is limited and dependent on both concentration of drug and treatment period. In vivo results demonstrated that IFN-α present antiviral action on Oropouche and Guaroa viruses when used as a prophylactic treatment. Moreover, a treatment initiated 3h after infection prevented the death of Guaroa virus infected-mice. Additionally, mortality of mice was related to the migration and replication of viruses in their brains. Our results suggest that IFN-α could be potentially useful in the prevention of diseases caused by Oropouche virus and in the prevention and/or treatment of diseases caused by Guaroa virus.


title: Feline Respiratory Extramedullary Plasmacytoma with Lymph Node Metastasis and Intrahistiocytic Amyloid

text: Summary A 14-year-old domestic longhaired cat presented with a 2-year history of nasal discharge and a recent onset of inappetence and submandibular lymphadenopathy. The cat was humanely destroyed after developing severe respiratory distress. Necropsy examination revealed thickened nasal turbinates and soft palate, and friable red–tan material within the frontal sinus, nasal cavity and nasopharynx. The lungs contained multifocal irregular friable tan nodules. Multiple lymph nodes were enlarged, friable and red–tan in colour. Histopathology revealed a mature type extramedullary plasmacytoma (EMP) within the frontal sinus, nasal cavity, soft palate, larynx, trachea, lungs and multiple lymph nodes. The lymph nodes and larynx also contained marked granulomatous inflammation with extensive intrahistiocytic (and lesser amounts of extracellular) lambda light chain amyloid, confirmed by electron microscopy and immunohistochemistry. Neoplastic cells expressed CD79a and MUM1. This is the first report of an infiltrative EMP of the feline respiratory tract with lymph node metastasis and predominantly intrahistiocytic amyloid.


title: Sleep during naturally occurring respiratory infections: A pilot study

text: Abstract There is strong experimental support that infections increase the drive for sleep in animals, and it is widely believed that more sleep is part of an adaptive immune response. While respiratory infections (RI) are very prevalent in humans, there is a striking lack of systematic knowledge on how it affects sleep. We recruited 100 people, among whom 28 became sick with an RI during the study period (fulfilling criteria for influenza-like illness, ILI, or acute respiratory infection, ARI). We measured sick participants’ sleep at home, both objectively (actigraphy) and subjectively (diary ratings), for one week as well as four weeks later when healthy. During the week with RI, people spent objectively longer time in bed and had a longer total sleep time compared to the healthy week. During the infection, participants also had more awakenings, but no significant differences in sleep latency or sleep efficiency. While sick, people also reported increased difficulties falling asleep, worse sleep quality, more restless sleep and more shallow sleep, while they did not report sleep to be less sufficient. Most problems occurred at the beginning of the sickness week, when symptoms were strong, and showed signs of recovery thereafter (as indicated by interactions between condition and day/night of data collection for all the 10 sleep outcomes). The degree of symptoms of RI was related to a worse sleep quality and more restless sleep, but not to any of the objective sleep outcomes or the other subjective sleep variables. Having a higher body temperature was not significantly related to any of the sleep variables. This study suggests that having a respiratory infection is associated with spending more time in bed and sleeping longer, but also with more disturbed sleep, both objectively and subjectively. This novel study should be seen as being of pilot character. There is a need for larger studies which classify pathogen type and include baseline predictors, or that manipulate sleep, in order to understand whether the sleep alterations seen during infections are adaptive and whether sleep interventions could be used to improve recovery from respiratory infections.


title: Complete Genome Sequence of Human Coronavirus NL63 CN0601/14, First Isolated in South Korea

text: We report here the complete genome sequence of the human coronavirus NL63 CN0601/14 strain, first isolated from South Korea. It contains 18-nucleotide discontinuous deletions of the open reading frame 1a (ORF1a) and spike regions. This study will aid in our understanding of the complete genome sequences of isolated coronaviruses in South Korea.


title: Quality control implementation for universal characterization of DNA and RNA viruses in clinical respiratory samples using single metagenomic next-generation sequencing workflow

text: BACKGROUND: In recent years, metagenomic Next-Generation Sequencing (mNGS) has increasingly been used for an accurate assumption-free virological diagnosis. However, the systematic workflow evaluation on clinical respiratory samples and implementation of quality controls (QCs) is still lacking. METHODS: A total of 3 QCs were implemented and processed through the whole mNGS workflow: a no-template-control to evaluate contamination issues during the process; an internal and an external QC to check the integrity of the reagents, equipment, the presence of inhibitors, and to allow the validation of results for each sample. The workflow was then evaluated on 37 clinical respiratory samples from patients with acute respiratory infections previously tested for a broad panel of viruses using semi-quantitative real-time PCR assays (28 positive samples including 6 multiple viral infections; 9 negative samples). Selected specimens included nasopharyngeal swabs (n = 20), aspirates (n = 10), or sputums (n = 7). RESULTS: The optimal spiking level of the internal QC was first determined in order to be sufficiently detected without overconsumption of sequencing reads. According to QC validation criteria, mNGS results were validated for 34/37 selected samples. For valid samples, viral genotypes were accurately determined for 36/36 viruses detected with PCR (viral genome coverage ranged from 0.6 to 100%, median = 67.7%). This mNGS workflow allowed the detection of DNA and RNA viruses up to a semi-quantitative PCR Ct value of 36. The six multiple viral infections involving 2 to 4 viruses were also fully characterized. A strong correlation between results of mNGS and real-time PCR was obtained for each type of viral genome (R(2) ranged from 0.72 for linear single-stranded (ss) RNA viruses to 0.98 for linear ssDNA viruses). CONCLUSIONS: Although the potential of mNGS technology is very promising, further evaluation studies are urgently needed for its routine clinical use within a reasonable timeframe. The approach described herein is crucial to bring standardization and to ensure the quality of the generated sequences in clinical setting. We provide an easy-to-use single protocol successfully evaluated for the characterization of a broad and representative panel of DNA and RNA respiratory viruses in various types of clinical samples. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3446-5) contains supplementary material, which is available to authorized users.


title: Sustaining Interferon Induction by a High-Passage Atypical Porcine Reproductive and Respiratory Syndrome Virus Strain

text: Porcine reproductive and respiratory syndrome virus (PRRSV) strain A2MC2 induces type I interferons in cultured cells. The objective of this study was to attenuate this strain by serial passaging in MARC-145 cells and assess its virulence and immunogenicity in pigs. The A2MC2 serially passaged 90 times (A2MC2-P90) retains the feature of interferon induction. The A2MC2-P90 replicates faster with a higher virus yield than wild type A2MC2 virus. Infection of primary pulmonary alveolar macrophages (PAMs) also induces interferons. Sequence analysis showed that the A2MC2-P90 has genomic nucleic acid identity of 99.8% to the wild type but has a deletion of 543 nucleotides in nsp2. The deletion occurred in passage 60. The A2MC2-P90 genome has a total of 35 nucleotide variations from the wild type, leading to 26 amino acid differences. Inoculation of three-week-old piglets showed that A2MC2-P90 is avirulent and elicits immune response. Compared with Ingelvac PRRS(®) MLV strain, A2MC2-P90 elicits higher virus neutralizing antibodies. The attenuated IFN-inducing A2MC2-P90 should be useful for development of an improved PRRSV vaccine.


title: A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity

text: Abstract The mammarenavirus Lassa (LASV) is highly prevalent in West Africa where it infects several hundred thousand individuals annually resulting in a high number of Lassa fever (LF) cases, a febrile disease associated with high morbidity and significant mortality. Mounting evidence indicates that the worldwide-distributed prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance. There are not Food and Drug Administration (FDA) licensed vaccines and current anti-mammarenavirus therapy is limited to an off-label use of ribavirin that is only partially effective and can cause significant side effects. Therefore, there is an unmet need for novel antiviral drugs to combat LASV. This task would be facilitated by the implementation of high throughput screens (HTS) to identify inhibitors of the activity of the virus ribonucleoprotein (vRNP) responsible for directing virus RNA genome replication and gene transcription. The use of live LASV for this purpose is jeopardized by the requirement of biosafety level 4 (BSL4) containment. We have developed a virus-free cell platform, where expression levels of reporter genes serve as accurate surrogates of vRNP activity, to develop cell-based assays compatible with HTS to identify inhibitors of LASV and LCMV mammarenavirus vRNP activities.


title: Disease embryo development network reveals the relationship between disease genes and embryo development genes

text: Abstract A basic problem for contemporary biology and medicine is exploring the correlation between human disease and underlying cellular mechanisms. For a long time, several efforts were made to reveal the similarity between embryo development and disease process, but few from the system level. In this article, we used the human protein–protein interactions (PPIs), disease genes with their classifications and embryo development genes and reconstructed a human disease-embryo development network to investigate the relationship between disease genes and embryo development genes. We found that disease genes and embryo development genes are prone to connect with each other. Furthermore, diseases can be categorized into three groups according to the closeness with embryo development in gene overlapping, interacting pattern in PPI network and co-regulated by microRNAs or transcription factors. Embryo development high-related disease genes show their closeness with embryo development at least in three biological levels. But it is not for embryo development medium-related disease genes and embryo development low-related disease genes. We also found that embryo development high-related disease genes are more central than other disease genes in the human PPI network. In addition, the results show that embryo development high-related disease genes tend to be essential genes compared with other diseases’ genes. This network-based approach could provide evidence for the intricate correlation between disease process and embryo development, and help to uncover potential mechanisms of human complex diseases.


title: Challenges of SARS-CoV-2 and lessons learnt from SARS in Guangdong Province, China

text: Abstract With lessons learnt from the SARS outbreak in 2003, Guangdong Province is taking the lead in bringing COVID-19 under control by multiple strict regulations in combination with effective healthcare provision.


title: L’Émergence du virus EBOLA chez l’homme: un long processus pas totalement élucidé

text: SUMMARY Since 1976 Ebola virus regularly has caused small deadly outbreaks in Central Africa, usually controlled in a few months. For the first time, an Ebola epidemic of exceptional magnitude dramatically engulfed several countries in West Africa since December 2013. Major failures of implementing measures to prevent human-to-human transmissions are the main cause of this large-scale Ebola outbreak. After about one-week incubation period, the Ebola virus disease is characterized by a sudden onset of high fever leading to multiple hemorrhages and to widespread organ failure. Several bat species constitute the main reservoirs of Ebola viruses. Human contamination would occur either directly from bats, widely consumed by the local populations, or through animal species susceptible to Ebola infection, such as chimpanzees and gorillas. Alongside this “natural cycle”, an “epidemic cycle” involving domestic animals living in villages such as dogs or pigs, is seriously suggested. Thus, according to the diversity of concerned animals and their clinical infection form, modalities of human contamination can be multiple and are still largely unknown. In this context, all efforts that could be made to unravel the mystery of the Ebola virus emergence in humans and clarify modalities of the virus transmission, would allow for predicting or for anticipating the future occurrence of epidemics. This review aims to provide an exhaustive inventory of the Ebola ecology to highlight events governing the virus transmission to humans that still remain unsolved.


title: Effective treatment strategies for paediatric community-acquired pneumonia

text: Pneumonia is the leading cause of death in children under 5 years of age worldwide and a cause of morbidity in a considerable number of children. A number of studies have sought to identify the ideal choice of antibiotics, route of administration and optimum duration of treatment based on the most likely aetiological agents. Emerging bacterial resistance to antibiotics is also an important consideration in treatment. However, inconsistent clinical and radiological definitions of pneumonia make comparison between studies difficult. There is also a lack of well designed adequately powered randomised controlled trials. This review describes the difficulties encountered in diagnosing community-acquired pneumonia, aetiology, treatment strategies with recommendations and highlights areas for further research.


2015: review of the year


title: Introduction: Perspectives on Democracy

text: This article explores diverse views on both the current challenges and limits as well as the reforms and innovations of existing democracies at the beginning of the twenty-first century. First, it argues that socioeconomic inequality, new populism, new forms of communication, and globalization have stimulated a renewal of interest in analyzing the “frontiers of democracy.” Democracies have reacted with different innovations and reforms in order to meet these challenges. The authors trace the phases of respective research from studies on singular, standalone instances to normative as well as empirical work on participatory (direct democratic and deliberative) systems. Finally, they advocate for combining the conceptual approach of defining democracy by the fulfillment of democratic values with rigorous empirical evaluation of the contributions (old and new) that institutions and procedures provide in order to fulfill these values and meet the mentioned challenges.


title: Chapter 132 Acute disseminated encephalomyelitis

text: Abstract The advent of magnetic resonance imaging (MRI) has contributed to increase the interest and awareness in childhood white matter disorders. Pediatric inflammatory demyelinating diseases of the central nervous system (CNS) are clinically heterogeneous with respect to their mode of presentation, clinical severity, rate of progression, and prognosis. Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory disorder of the CNS, typically transitory and self-limiting. The highest incidence of ADEM is observed during childhood. It is characterized by an acute encephalopathy with polyfocal neurological deficits. In the absence of specific biological markers the diagnosis of ADEM is still based on clinical features and MRI evidence of widespread demyelination, after ruling out other possible explanations for an acute encephalopathy. Over the past decade, many retrospective patient studies have focused on clinical and neuroimaging features, in an attempt to define specific diagnostic criteria. The occurrence of relapses in children with ADEM poses diagnostic difficulties in its differentiation from multiple sclerosis (MS) and neuromyelitis optica (NMO). With the widespread use of high-dose steroids, the long-term prognosis of ADEM with regard to functional and cognitive recovery is favorable. This chapter summarizes the available literature on ADEM in children, including the proposed consensus definitions for its monophasic and relapsing variants.


title: Dispositif de diagnostic et de gestion du risque d’épidémie de grippe chez les personnes âgées en Ehpad en région Paca, saisons grippales 2012–2013 et 2013–2014

text: Introduction Depuis l’hiver 2012–2013, l’Agence régionale de santé (ARS) Paca dote les établissements d’hébergement pour personnes âgées dépendantes (Ehpad) de la région d’écouvillons naso-pharyngés pour réaliser des tests rapides à orientation diagnostique (TROD) grippe. Une étude pluriannuelle a été initiée pour mieux cibler les virus circulant en Ehpad. Méthode En cas de grippe suspectée chez un résident, les Ehpad collectaient des données cliniques et un TROD était analysé par un laboratoire. Les prélèvements étaient ensuite analysés par RT-PCR multiplex au CHU de Marseille pour vérification des résultats et recherche d’autres virus (adénovirus, entérovirus [EV], parainfluenzavirus [PIV], influenzavirus, virus respiratoire syncitial [VRS], métapneumovirus [hMPV], rhinovirus et coronavirus [CoV]). Résultats Durant la première saison, 62 prélèvements ont été analysés. L’âge moyen des cas était de 87ans et 94 % étaient vaccinés contre la grippe saisonnière. Les délais moyen et médian de prélèvement étaient respectivement de 1,5 et 1 jour. Les TROD grippe étaient positifs dans 23 % des prélèvements. Les RT-PCR ont identifié un virus pour 52 % des prélèvements dont 55 % de virus grippal. Les autres virus (45 %) étaient des EV, PIV, VRS, hMPV et CoV. Discussion La RT-PCR a permis de doubler le nombre de résultats positifs, tous virus confondus, 50 % des prélèvements étant positifs pour un des virus recherchés. Le délai maximal de prélèvement de 48h nécessaire à l’interprétation correcte des TROD était respecté. Peu de prélèvements ont été collectés sur la saison 2013–2014, du fait d’une épidémie grippale d’intensité limitée chez les personnes âgées, et les résultats de la surveillance seront disponibles au printemps. Cette étude sera renouvelée sur plusieurs années.


title: The Murray Valley encephalitis virus prM protein confers acid resistance to virus particles and alters the expression of epitopes within the R2 domain of E glycoprotein

text: Abstract To study the role of the precursor to the membrane protein (prM) in flavivirus maturation, we inhibited the proteolytic processing of the Murray Valley encephalitis (MVE) virus prM to membrane protein in infected cells by adding the acidotropic agent ammonium chloride late in the virus replication cycle. Viruses purified from supernatants of ammonium chloride-treated cells contained prM protein and were unable to fuse C6/36 mosquito cells from without. When ammonium chloride was removed from the cells, both the processing of prM and the fusion activity of the purified viruses were partially restored. By using monoclonal antibodies (MAbs) specific for the envelope (E) glycoprotein of MVE virus, we found that at least three epitopes were less accessible to their corresponding antibodies in the prM-containing MVE virus particles. Amino-terminal sequencing of proteolytic fragments of the E protein which were reactive with sequence-specific peptide antisera or MAb enabled us to estimate the site of the E protein interacting with the prM to be within amino acids 200 to 327. Since prM-containing viruses were up to 400-fold more resistant to a low pH environment, we conclude that the E-prM interaction might be necessary to protect the E protein from irreversible conformational changes caused by maturation into the acidic vesicles of the exocytic pathway.


title: Gallus gallus domesticus are resistant to infection with Neospora caninum tachyzoites of the NC-1 strain

text: The aim of this study was to experimentally evaluate infection in Gallus gallus domesticus with Neospora caninum tachyzoites of the NC-1 strain. Experimental infection was conducted in 90-day-old chickens, embryonated eggs and bioassays in dogs. In the first experiment, poults were randomly divided into four groups. Groups I and II were provided feed with coccidiostat, whereas groups III and IV received feed without coccidiostat. When the poults from groups I and III reached 90 days of age, they received a subcutaneous inoculation of N. caninum. Once the hens entered their egg-laying period, during the following 30 days, the eggs were collected, identified, weighed and placed in an incubator. On the 70th day after inoculation, all animals, including the chicks, were euthanized. Tissue samples from the adult poultry and chicks were collected for histopathology, immunohistochemistry (IHC) and PCR. Brain tissue and pectoral muscle samples from infected birds were fed to two dogs. Notably, the average weight of the group III eggs was lower than that of the group IV eggs (p < 0.05). No changes consistent with infection in adult poultry or chicks were detected by histopathology or IHC; moreover, no amplified parasite DNA was detected in the birds’ tissues or dogs’ feces. No dog eliminated oocysts. In the second experiment, the embryonated chicken eggs were inoculated with 1 × 10(2)N. caninum tachyzoites, on the 10th day of incubation, and chicks born from these eggs were housed in boxes suitable for the species and received commercial feed and distilled water ad libitum. On the 30th day after infection (DAI), the poultry were euthanized, and their organs were processed as described in experiment I. The amplification of parasite DNA was observed in the spleen and pectoral muscles of one of the birds. The ingestion of bird tissues by dogs did not result in oocyst elimination. These results indicate that the parasite may have been eliminated by the host and that the use of tachyzoites to induce chronic disease might be a poor source for hens.


title: New quaternary ammonium camphor derivatives and their antiviral activity, genotoxic effects and cytotoxicity

text: Abstract The synthesis and biological evaluation of a novel series of dimeric camphor derivatives are described. The resulting compounds were studied for their antiviral activity, cyto- and genotoxicity. Compounds 3a and 3d in which the quaternary nitrogen atoms are separated by the C5H10 and С9H18 aliphatic chain, exhibited the highest efficiency as an agent inhibiting the reproduction of the influenza virus A(H1N1)pdm09. The cytotoxicity data of compounds 3 and 4 revealed their moderate activity against malignant cell lines; compound 3f had the highest activity for the CEM-13 cells. These results show close agreement with the data of independent studies on toxicity of these compounds, in particular that the toxicity of compounds strongly depends on spacer length.


title: Pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model

text: Chronic lung allograft dysfunction (CLAD) is a serious complication after lung transplantation and thought to represent chronic rejection. Increased expression of Pentraxin 3 (PTX3), an acute phase protein, was associated with worse outcome in lung transplant patients. To determine the role of recipient PTX3 in development of chronic rejection, we used a minor alloantigen-mismatched murine orthotopic single lung transplant model. Male C57BL/10 mice were used as donors. Male PTX3 knockout (KO) mice and their wild type (WT) littermates on 129/SvEv/C57BL6/J background were used as recipients. In KO recipients, 7/13 grafted lungs were consolidated without volume recovery on CT scan, while only 2/9 WT mice showed similar graft consolidation. For grafts where lung volume could be reliably analyzed by CT scan, the lung volume recovery was significantly reduced in KO mice compared to WT. Interstitial inflammation, parenchymal fibrosis and bronchiolitis obliterans scores were significantly higher in KO mice. Presence of myofibroblasts and lymphoid aggregation was significantly enhanced in the grafts of PTX3 KO recipients. Recipient PTX3 deficiency enhanced chronic rejection-like lesions by promoting a fibrotic process in the airways and lung parenchyma. The underlying mechanisms and potential protective role of exogenous PTX3 as a therapy should be further explored.


The Wounded Healer: A Narrative Review of the Mental Health Effects of the COVID-19 Pandemic on Healthcare Workers


title: Development of A Loop-Mediated Isothermal Amplification (LAMP) for the Detection of F5 Fimbriae Gene in Enterotoxigenic Escherichia coli (ETEC)

text: The objective of this study was to establish a loop-mediated isothermal amplification (LAMP) method for the detection of F5 fimbriae gene in Enterotoxigenic Escherichia coli. A set of four primers were designed based on the conservative sequence of coding F5 fimbriae. Temperature and time condition, specificity test, and sensitivity test were performed with the DNA of Escherichia coli (F5+). The results showed that the optimal reaction condition for LAMP was achieved at 61 °C for 45 min in a water bath. Ladder-like products were produced with those F5-positive samples by LAMP, while no product was generated with other negative samples. The assay of LAMP had a detection limit equivalent to 72 cfu/tube, which was more sensitive than PCR (7.2 × 10(2) cfu/tube). The agreement rate between LAMP and PCR was 100 % in detecting simulation samples. Thus, the LAMP assay may be a new method for rapid detection of F5 fimbriae gene of ETEC.


title: A systemic approach to assess the potential and risks of wildlife culling for infectious disease control

text: The maintenance of infectious diseases requires a sufficient number of susceptible hosts. Host culling is a potential control strategy for animal diseases. However, the reduction in biodiversity and increasing public concerns regarding the involved ethical issues have progressively challenged the use of wildlife culling. Here, we assess the potential of wildlife culling as an epidemiologically sound management tool, by examining the host ecology, pathogen characteristics, eco-sociological contexts, and field work constraints. We also discuss alternative solutions and make recommendations for the appropriate implementation of culling for disease control.


title: A systematic review on use of aminoquinolines for the therapeutic management of COVID-19: Efficacy, safety and clinical trials

text: Recent global outbreak of the pandemic caused by coronavirus (COVID-19) emphasizes the urgent need for novel antiviral therapeutics. It can be supplemented by utilization of efficient and validated drug discovery approaches such as drug repurposing/repositioning. The well reported and clinically used anti-malarial aminoquinoline drugs (chloroquine and hydroxychloroquine) have shown potential to be repurposed to control the present pandemic by inhibition of COVID-19. The review elaborates the mechanism of action, safety (side effects, adverse effects, toxicity) and worldwide clinical trials for chloroquine and hydroxychloroquine to benefit the clinicians, medicinal chemist, pharmacologist actively involved in the management of COVID-19 infection.


title: Understanding the early dynamics of the 2014 porcine epidemic diarrhea virus (PEDV) outbreak in Ontario using the incidence decay and exponential adjustment (IDEA) model

text: BACKGROUND: The United States swine industry was first confronted with porcine epidemic diarrhea virus (PEDV) in 2013. In young pigs, the virus is highly pathogenic and the associated morbidity and mortality has a significant negative impact on the swine industry. We have applied the IDEA model to better understand the 2014 PEDV outbreak in Ontario, Canada. Using our simple, 2-parameter IDEA model, we have evaluated the early epidemic dynamics of PEDV on Ontario swine farms. RESULTS: We estimated the best-fit R(0) and control parameter (d) for the between farm transmission component of the outbreak by fitting the model to publically available cumulative incidence data. We used maximum likelihood to compare model fit estimates for different combinations of the R(0) and d parameters. Using our initial findings from the iterative fitting procedure, we projected the time course of the epidemic using only a subset of the early epidemic data. The IDEA model projections showed excellent agreement with the observed data based on a 7-day generation time estimate. The best-fit estimate for R(0) was 1.87 (95% CI: 1.52 – 2.34) and for the control parameter (d) was 0.059 (95% CI: 0.022 – 0.117). Using data from the first three generations of the outbreak, our iterative fitting procedure suggests that R(0) and d had stabilized sufficiently to project the time course of the outbreak with reasonable accuracy. CONCLUSIONS: The emergence and spread of PEDV represents an important agricultural emergency. The virus presents a significant ongoing threat to the Canadian swine industry. Developing an understanding of the important epidemiological characteristics and disease transmission dynamics of a novel pathogen such as PEDV is critical for helping to guide the implementation of effective, efficient, and economically feasible disease control and prevention strategies that are able to help decrease the impact of an outbreak.


title: Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study

text: BACKGROUND: COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital. Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes. METHODS: We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020. The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h. Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation. FINDINGS: All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet–fibrin thrombi (in 33 cases). The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases). Electron microscopy revealed that viral particles were predominantly located in the pneumocytes. INTERPRETATION: The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent. Importantly, the presence of platelet–fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy. FUNDING: None.


title: Lymphoproliferative responses and protection in conventional piglets inoculated orally with virulent or attenuated porcine epidemic diarrhoea virus

text: Abstract Lymphocyte proliferative responses were evaluated in mucosal (mesenteric lymph nodes) and systemic (spleen and blood) lymphoid tissues of conventional piglets inoculated with the virulent or attenuated isolates of porcine epidemic diarrhoea virus (PEDV) strain CV-777 and challenged 21 days later with the virulent isolate of the same virus. A lymphoproliferative assay was developed in which mononuclear cells isolated from lymphoid tissues at different postinoculation and postchallenge days underwent a secondary in vitro stimulation with semipurified antigen obtained from PEDV-infected cell cultures. Vigorous lymphocyte proliferative responses were detected in the pigs inoculated with the virulent PEDV at postinoculation days 4–21, especially in the mesenteric lymph nodes and the blood; however, in the spleen this response was lower and less regular. The pigs inoculated with the attenuated virus showed a less intense response, the higher lymphocyte proliferation also corresponded to the mononuclear cells from mesenteric lymph nodes. Lymphocyte proliferation responses showed high correlations with protection against homologous challenge with virulent PEDV, and this correlation was higher in the gut associated lymphoid tissues (mesenteric lymph nodes). The cell proliferation response detected in blood mirrored that detected in the mesenteric lymph nodes, and showed also good correlation with protection. The results confirm that T-cell-helper function, assessed by lymphocyte proliferation responses, contributes to establishing a protective immune response against PEDV infections.


title: Kicking on while it’s still kicking off – getting surgery and anaesthesia restarted after COVID‐19

text: The UK National Health Service (NHS) has risen to the challenge posed by COVID-19 through Herculean efforts to expand capacity. This has included doubling or trebling intensive care (ICU) capacity within hospitals, augmenting this with Nightingale Hospitals, cancelling all non-emergency surgery and redeploying staff and equipment to focus on a single disease. At the same time, government and population efforts have - through social distancing then lockdown- successfully flattened the epidemic curve and so reduced demand. Together, these actions have enabled treatment of all those needing hospital care for COVID-19 and avoided the unfettered increase in mortality that would have accompanied an overwhelmed healthcare service.


title: Inactivation photochimique des pathogènes des plaquettes et du plasma : cinq ans d’utilisation clinique de routine et d’hémovigilance. Vers un changement de paradigme de la sécurité en transfusion

text: Résumé La transfusion des produits sanguins labiles demeure une thérapeutique essentielle, efficace et vitale, en l’absence d’alternative thérapeutique. La transmission d’agents infectieux pathogènes par la transfusion du sang, des produits sanguins labiles et des médicaments dérivés du sang a toujours été redoutée à juste titre par les malades et les médecins. L’inactivation photochimique des concentrés plaquettaires et du plasma, par une technique associant l’amotosalen et les UVA, a été utilisée pendant cinq ans dans une région française pour toute la population et sur un large spectre de patients, avec efficacité et sécurité. Il semblerait opportun de mettre en place les produits sanguins labiles ayant subi une inactivation des pathogènes par une technique qui a déjà été approuvée réglementairement et de ne pas attendre un système parfait étendu aux concentrés de globules rouges. La mise en place universelle de l’inactivation des pathogènes dans les produits sanguins labiles est une étape majeure et clé de la sécurité infectieuse en transfusion. Abstract The transfusion of labile blood products is vital and essential for patients in absence of alternative treatment. Patients and doctors have always feared transfusion-transmitted infections by blood, blood components and blood-derived drugs. Photochemical inactivation of platelet concentrates and plasma, using a technique associating amotosalen and UVA, has been used for five years in a French region for the whole population and a large spectrum of patients, with efficacy and safety. It would seem wise to introduce labile blood products, submitted to pathogen inactivation by a technique already approved by a regulatory agency and not to wait for a perfect system including red blood cells concentrates. Universal implementation of pathogen inactivation in labile blood products is a major and key step to improve safety against infection in transfusion.


title: Collectivités : lieu de rencontre virale

text: It is well known that young infants attending day-care centers are subjected to repeated infectious episodes, with a tendency to involve the respiratory and gastrointestinal tracts. Their long-term impact is difficult to assess because there are few relevant prospective studies. The risk of infection is influenced in part by the structure of the day-care center, and it is more important in the early months of attending and linked to later recurrent infectious episodes. Causal links between viral infection and asthma are complex. Viral infections increase the risk of asthma exacerbation but the presence of asthma also increases the risk of severe responses to a viral infection. While infections acquired in this environment are mainly viral, their recurrence can lead to excessive use of antibiotics which promote antimicrobial resistance with an impact on the digestive or respiratory microbiota.


title: MyD88 Is Required for Protection from Lethal Infection with a Mouse-Adapted SARS-CoV

text: A novel human coronavirus, SARS-CoV, emerged suddenly in 2003, causing approximately 8000 human cases and more than 700 deaths worldwide. Since most animal models fail to faithfully recapitulate the clinical course of SARS-CoV in humans, the virus and host factors that mediate disease pathogenesis remain unclear. Recently, our laboratory and others developed a recombinant mouse-adapted SARS-CoV (rMA15) that was lethal in BALB/c mice. In contrast, intranasal infection of young 10-week-old C57BL/6 mice with rMA15 results in a nonlethal infection characterized by high titer replication within the lungs, lung inflammation, destruction of lung tissue, and loss of body weight, thus providing a useful model to identify host mediators of protection. Here, we report that mice deficient in MyD88 (MyD88(−/−)), an adapter protein that mediates Toll-like receptor (TLR), IL-1R, and IL-18R signaling, are far more susceptible to rMA15 infection. The genetic absence of MyD88 resulted in enhanced pulmonary pathology and greater than 90% mortality by day 6 post-infection. MyD88(−/−) mice had significantly higher viral loads in lung tissue throughout the course of infection. Despite increased viral loads, the expression of multiple proinflammatory cytokines and chemokines within lung tissue and recruitment of inflammatory monocytes/macrophages to the lung was severely impaired in MyD88(−/−) mice compared to wild-type mice. Furthermore, mice deficient in chemokine receptors that contribute to monocyte recruitment to the lung were more susceptible to rMA15-induced disease and exhibited severe lung pathology similar to that seen in MyD88(−/−)mice. These data suggest that MyD88-mediated innate immune signaling and inflammatory cell recruitment to the lung are required for protection from lethal rMA15 infection.


title: Protracted course of coronavirus disease with severe acute respiratory distress syndrome: a case report

text: BACKGROUND: Coronavirus Disease (COVID‐19) is a growing concern worldwide. About 5% of COVID‐19 cases require intensive care. However, the optimal treatment for respiratory failure in COVID‐19 patients is yet to be determined. CASE PRESENTATION: A 79‐year‐old man with severe acute respiratory distress syndrome due to COVID‐19 was admitted to our intensive care unit. Prone ventilation was effective in treating the patient’s hypoxemia. Further, the patient received lung protective ventilation with a tidal volume of 6–8 mg/kg (predicted body weight). However, the patient’s respiratory failure did not improve and he died 16 days after admission because of multiple organ failure. Serial chest computed tomography revealed a change from ground‐glass opacity to consolidation pattern in both lungs. CONCLUSIONS: We report a protracted case of COVID‐19 in a critically ill patient in Japan. Although prone ventilation may contribute to treating hypoxemia, its efficacy in preventing mortality from COVID‐19 is unknown.


title: Porcine Epidemic Diarrhea Altered Colonic Microbiota Communities in Suckling Piglets

text: Porcine epidemic diarrhea (PED) is a major gastrointestinal disease afflicting suckling pigs that causes huge industrial economic losses. In this study, we investigated microbiota from the colonic mucosa and content in healthy and PED piglets. High-throughput 16S rRNA gene sequencing was performed to identify inter-group differences. Firmicutes, Fusobacteria, Proteobacteria, and Bacteroidetes were the top four affected phyla. The proportion of Proteobacteria was higher in infected than in healthy piglets, and the opposite was observed for Bacteroidetes (more than four-fold higher in the healthy group). In the infected group, Fusobacterium accounted for 36.56% and 21.61% in the colonic mucosa and contents, respectively, while in the healthy group, they comprised 22.53% and 12.67%, respectively. The percentage of Lactobacillus in healthy colons (15.63%) was considerably higher than that in the disease group (<10%). In both the colonic mucosa and contents, functional enrichment differed significantly between healthy and diseased groups. Overall, infection with the PED virus increased the proportion of harmful bacteria and decreased the proportion of beneficial bacteria in the colons of piglets. Targeting intestinal microbiota could be a promising method for PED prevention, thus opening new avenues for future research.


title: Chapter 12 Style and Usage for Life Science

text: Publisher Summary This chapter provides guidelines for manuscript preparation of life science journals. The rules for writing in life science are consistent with those in earth and environmental sciences and medical science. As with all scientific writing, it is important to research the specific needs and preferences of the journal to which the manuscript is being sent. This will not only ease the writing process, but will also increase the chances of publication. This chapter explains biochemical nomenclature and abbreviations used in life science. In addition, it includes a list of preferred units in the life sciences. In scientific writing, especially in the United States, articles dealing with life science issues are appearing much less frequently than those in other scientific disciplines.


title: Perspectives on the epizootiology of feline enteric coronavirus and the pathogenesis of feline infectious peritonitis

text: Abstract This review presents some current thoughts regarding teh epizootiology of the feline coronaviruses; feline infectious peritonisis virus (FIPV) and feline coronavirus (FEVC), with primary emphasis on the pathogenesis of these viruses in nature. Although the mechanism(s) whereby FIPV causes disease are still incompletely understood, there have been significant contributions to the literature over the past decade which provide a framework upon which plausible explanations can be postulated. Two concepts are presented which attempt to clarify the pathogenesis of FIPV and at the same time may serve as an impetus for further research. The first involves the hypothesis, originally promulgated by Pedersen in 19891, that FIPV is derived from FECV during virus replication in the gastrointestinal tract. The second involves a unique mechanism of the mucosal immune system referred to as oral tolerance, which under normal conditions promotes the production of secretory immunity and suppresses the production of systematic immunity. In the case of FIPV infection, we propose that oral tolerance is important in the control of the virus at the gastrointestinal tract level. Once oral tolerance is disrupted, FIPV is capable of systemic spread resulting in immune-mediated vasculitis and death. Thus, it may be that clinical forms of FIP are due to a combination of two events, the first being the generation of FIPV from FECV, and the second being the capacity of FIPV to circumvent oral tolerance.


title: Trypsin-induced hemagglutination activity of porcine epidemic diarrhea virus

text: The hemagglutination (HA) activity of porcine epidemic diarrhea virus (PEDV) was investigated. Two cell-adapted strains of PEDV (KPEDV-9 and SM98LVec) were subjected to HA test against erythrocytes of various origin. Both strains showed HA activity with rabbit erythrocytes only after treatment with trypsin or neuraminidase. Optimal conditions for inducing HA activity of PEDV were 2 h incubation at 37°C using phosphate-buffered saline containing 0.1% BSA. These results suggest that the HA activity of PEDV is most likely caused by proteolytic action on it, which could be developed as a new diagnostic method to rapidly detect and differentiate PEDV infections from other enteric diseases.


title: Medical Geology

text: The relationship between geology and healing was recognized by ancient people, and medical geology was a popular subject that engaged famous scholars, trained as physicians, from the late-18th to mid-19th centuries. Acceptance of germ theory around 1850 as a major factor in human health shifted the attention to microbes that led to a period of dormancy for medical geology. However, since the 1950s with the advent of precise and accurate analytical techniques, aided by fast computers, geochemists have been able to establish the link between geologic environment and incidence of disease in populations. Medical geology experienced a resurgence around the 1960s, leading to establishment of professional medical geology organizations, specialized courses at universities and colleges, national and international conferences, publication of textbooks, journals, and atlases. This article presents a historical review of medical geology, its evolution, scope and future prospects. Basic principles of medical geology are described and examples of various trace elements on human, and animal health presented. The role of clays in healing and ingestion of clays by humans and animals is examined. Grave and increasing health problems associated with climate change and air pollution from dust and other materials and their impacts on human and ecological health are discussed. Finally, areas of multidisciplinary research opportunities for medical geologists and collaboration with other health, social, and behavioral scientists are identified.


title: Risk factors for disease progression in mild to moderate COVID-19 patients– a multi-center observational study

text: OBJECTIVES: Since December 2019, patients infected with a novel coronavirus disease (COVID-19) emerged in Wuhan city and rapidly spread globally. The risk for poor outcome dramatically increases once a patient progressed to the severe or critical stage. The present study aims to investigate the risk factors for disease progression in mild to moderate cases of COVID-19. METHODS: We conducted a cohort study which included 1007 mild to moderate cases with COVID-19 from 3 hospitals in Wuhan. Clinical characteristics and baseline laboratory findings were collected. Patients had been followed up for 28 days for observation of disease progression. The endpoint was the progression to a more severe disease stage. RESULTS: During a follow up of 28 days, 720 patients (71.50%) had recovered or been symptomatically stable, 222 patients (22.05%) had progressed to the severe stage, 22 patients (2.18%) had progressed to the critically ill stage, 43 patients (4.27%) had deceased. Multivariate Cox proportional hazards models identified that increased age (HR 2.56, 95% CI 1.97 to 3.33), male sex (HR 1.79, 95% CI 1.41 to 2.28), presence of hypertension (HR 1.44, 95% CI 1.11 to 1.88), diabetes (HR 1.82, 95% CI 1.35 to 2.44), chronic obstructive pulmonary disease (HR 2.01, 95% CI 1.38 to 2.93) and coronary artery disease (HR 1.83, 95% CI 1.26 to 2.66) were risk factors for disease progression. History of smoking was protective against disease progression (HR 0.56, 95% CI 0.34 to 0.91). Elevated procalcitonin (HR 1.72, 95% CI 1.02 to 2.90), urea nitrogen (HR 1.72, 95% CI 1.21 to 2.43), α-hydroxybutyrate dehydrogenase (HR 3.02, 95% CI 1.26 to 7.21) and D-dimer (HR 2.01, 95% CI 1.12 to 3.58) at baseline were also associated with risk for disease progression. CONCLUSIONS: This study identified a panel of risk factors for disease progression in mild to moderate cases with COVID-19.


title: Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study

text: AIMS/HYPOTHESIS: Hyperglycaemia is associated with an elevated risk of mortality in community-acquired pneumonia, stroke, acute myocardial infarction, trauma and surgery, among other conditions. In this study, we examined the relationship between fasting blood glucose (FBG) and 28-day mortality in coronavirus disease 2019 (COVID-19) patients not previously diagnosed as having diabetes. METHODS: We conducted a retrospective study involving all consecutive COVID-19 patients with a definitive 28-day outcome and FBG measurement at admission from 24 January 2020 to 10 February 2020 in two hospitals based in Wuhan, China. Demographic and clinical data, 28-day outcomes, in-hospital complications and CRB-65 scores of COVID-19 patients in the two hospitals were analysed. CRB-65 is an effective measure for assessing the severity of pneumonia and is based on four indicators, i.e. confusion, respiratory rate (>30/min), systolic blood pressure (≤90 mmHg) or diastolic blood pressure (≤60 mmHg), and age (≥65 years). RESULTS: Six hundred and five COVID-19 patients were enrolled, including 114 who died in hospital. Multivariable Cox regression analysis showed that age (HR 1.02 [95% CI 1.00, 1.04]), male sex (HR 1.75 [95% CI 1.17, 2.60]), CRB-65 score 1–2 (HR 2.68 [95% CI 1.56, 4.59]), CRB-65 score 3–4 (HR 5.25 [95% CI 2.05, 13.43]) and FBG ≥7.0 mmol/l (HR 2.30 [95% CI 1.49, 3.55]) were independent predictors for 28-day mortality. The OR for 28-day in-hospital complications in those with FBG ≥7.0 mmol/l and 6.1–6.9 mmol/l vs <6.1 mmol/l was 3.99 (95% CI 2.71, 5.88) or 2.61 (95% CI 1.64, 4.41), respectively. CONCLUSIONS/INTERPRETATION: FBG ≥7.0 mmol/l at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes. Glycaemic testing and control are important to all COVID-19 patients even where they have no pre-existing diabetes, as most COVID-19 patients are prone to glucose metabolic disorders. [Figure: see text]


China revises law on infectious diseases


Dual protection for day care procedures: Need in Coronavirus Disease 2019 (COVID‐19) pandemic


title: The association between age, COVID-19 symptoms, and social distancing behavior in the United States

text: BACKGROUND: Public health authorities recommend that people practice social distancing, especially if they have symptoms of coronavirus disease (COVID-19), or are older and more at risk of serious illness if they become infected. We test the hypothesis that these groups are following these recommendations and are more likely to undertake social distancing. METHODS: We conducted an open online survey of 4,676 U.S. adults aged 18 and older between April 4 and April 7, 2020. We model the effects of age and common COVID-19 symptoms in the last two weeks on going out of the home for non-healthcare reasons the day before taking the survey, using a logistic model and the number of close contacts (within 6 feet) that respondents had with non-household members, using a Poisson count model. Our models control for several covariates, including other flu-like symptoms, sex, education, income, whether the respondent worked in February, household size, population density in the respondent’s ZIP code, state fixed effects, and the day of completion of the survey. We also weight our analyses to make the sample representative of the U.S. adult population. FINDINGS: About 52 percent of the adult United States population went out of their home the previous day. On average, adults had close contact with 1.9 non-household members. We find that having at least one COVID-19 symptom (fever, dry cough, or shortness of breath) increased the likelihood of going out the previous day and having additional close contacts with non-household members; however, the estimates were not statistically significant. When disaggregating our analysis by COVID-19 symptoms, we find no strong evidence of greater social distancing by people with a fever or cough in the last two weeks, but we do find that those who experienced shortness of breath have fewer close contacts, with an incidence rate ratio (IRR) of 0.49 (95% CI: 0.30–0.78). Having other flu-like symptoms reduces the odds of going out by 0.32 (95% CI: 0.18–0.60) and the incidence rate of having close contacts by 42 percent (IRR = 0.58; 95% CI: 0.38–0.88). We find that older people are just as likely to leave their homes as younger people, but people over the age of 50 had less than half the predicted number of close contacts than those who were younger than 30. Our approach has the limitation that the survey sample is self-selected. Our findings may therefore be subject to selection bias that is not adequately controlled for by weighting. In addition, the possibility exists of confounding of the results due to omitted variable bias. CONCLUSIONS: We provide evidence that older people are having significantly fewer close contacts than younger people, which is in line with the public health authorities’ recommendations. We also find that people experiencing shortness of breath are practicing more intense social distancing. However, we find that those with two other common COVID-19 symptoms, fever and dry cough, are not engaging in greater social distancing, suggesting that increased targeting on relevant symptoms, and messaging, may be required.


docid: evsxldng

title: Targeting and retention of Golgi membrane proteins

text: Abstract Recent cloning of genes encoding membrane proteins of the Golgi complex has allowed investigation of protein targeting to this organelle. Targeting signals have been identified in three glycosyltransferases, a viral envelope protein and several proteins of the trans-Golgi network. Interestingly, the targeting signals for membrane proteins of the Golgi stacks seem to be contained in transmembrane domains. Information in the cytoplasmic tails is required for the targeting of trans-Golgi network proteins. Mechanisms involving both retention and retrieval have been invoked.


title: CHAPTER 13 Retrovirus Evolution

text: ABSTRACT Retroviruses manifest a very rich ensemble of genome structures. The evolution of retroviruses varies enormously, with fixation rates varying by as much as a million fold. The emergence of novel genome structures follows remorselessly with the fixation of point mutations and is most apparent for the lentivirus subgroup that has burst on the scene recently. Accordingly, bio-logic suggests that new genome structures will emerge among the lentiviruses, most notably HIV-1.


Global status of Middle East respiratory syndrome coronavirus in dromedary camels: a systematic review – CORRIGENDUM


Impact of the Covid-19 Outbreak on the Clinical and Research Activities of Memory Clinics: An Alzheimer’s Disease Center Facing the Covid-19 Crisis


title: Chapter 91 FPR Ligands

text: ABSTRACT Formyl peptide receptors (FPRs) belong to the classical G protein-coupled chemoattractant receptor family. They are mainly expressed in mammalian phagocytic leukocytes and play important roles in inflammatory and immune responses. N-formyl peptides produced by Gram-negative bacteria were among the first chemotactic factors identified for two FPRs in human beings: FPR1 (originally termed FPR) and FPR2 (originally termed FPRL1). During the past few years, a variety of novel pathogen- and host-derived agonists as well as antagonists for the FPR family have been identified, indicating a broader spectrum of the biological significance of these receptors. Activation of FPRs in leukocytes by agonists induces cell chemotaxis, phagocytosis, release of proinflammatory mediators and gene transcription. Despite these new developments, the in vivo functions of FPRs and their ligands in disease states are not yet fully understood. This chapter summarizes the pharmacological characterization of FPR ligands and their implications in pathophysiological conditions.


docid: mqrrirln

title: Metformin: Sentinel of the Epigenetic Landscapes That Underlie Cell Fate and Identity

text: The biguanide metformin is the first drug to be tested as a gerotherapeutic in the clinical trial TAME (Targeting Aging with Metformin). The current consensus is that metformin exerts indirect pleiotropy on core metabolic hallmarks of aging, such as the insulin/insulin-like growth factor 1 and AMP-activated protein kinase/mammalian Target Of Rapamycin signaling pathways, downstream of its primary inhibitory effect on mitochondrial respiratory complex I. Alternatively, but not mutually exclusive, metformin can exert regulatory effects on components of the biologic machinery of aging itself such as chromatin-modifying enzymes. An integrative metabolo-epigenetic outlook supports a new model whereby metformin operates as a guardian of cell identity, capable of retarding cellular aging by preventing the loss of the information-theoretic nature of the epigenome. The ultimate anti-aging mechanism of metformin might involve the global preservation of the epigenome architecture, thereby ensuring cell fate commitment and phenotypic outcomes despite the challenging effects of aging noise. Metformin might therefore inspire the development of new gerotherapeutics capable of preserving the epigenome architecture for cell identity. Such gerotherapeutics should replicate the ability of metformin to halt the erosion of the epigenetic landscape, mitigate the loss of cell fate commitment, delay stochastic/environmental DNA methylation drifts, and alleviate cellular senescence. Yet, it remains a challenge to confirm if regulatory changes in higher-order genomic organizers can connect the capacity of metformin to dynamically regulate the three-dimensional nature of epigenetic landscapes with the 4th dimension, the aging time.


docid: hgkjnvby

title: Interoperability of population-based patient registries

text: Enabling full interoperability within and between population-based patient- registry domains would open up access to a rich and unique source of health data for secondary data usage. Previous attempts to tackle patient-registry interoperability have met with varying degrees of success, but a unifying solution remains elusive. The purpose of this paper is to show by practical example how a solution is attainable via the implementation of an existing framework based of the concept of federated, semantic metadata registries. One important feature motivating the use of this framework is that it can be implemented gradually and independently within each patient-registry domain. By employing linked open data principles, the framework extends the ISO/IEC 11179 standard to provide both syntactic and semantic interoperability of data elements with the means of specifying automated extraction scripts for retrieval of data from different registry content models. The examples provided address the domain of European population-based cancer registries to demonstrate the feasibility of the approach. One of the examples shows how quick gains are derivable by allowing retrieval of aggregated core data sets. The other examples show how aggregated full sets of data and record-level data might also be retrieved from each local registry. An infrastructure of patient-registry domains adhering to the principles of the framework would provide the semantic contexts and inter-linkage of data necessary for automated search and retrieval of registry data. It would thereby also lay the foundation for making registry data serviceable to artificial intelligence (AI) applications.


title: DESINFECTANTES Y ANTISÉPTICOS FRENTE AL CORONAVIRUS: SÍNTESIS DE EVIDENCIAS Y RECOMENDACIONES

text: Resumen Objetivo: Sintetizar la evidencia disponible sobre el uso de antisépticos y desinfectantes ante la infección de COVID-19 Método: Búsqueda bibliográfica en las principales bases de datos (WOS, CCC, DIIDW, KJD, MEDLINE, RSCI, SCIELO, PubMed, BMJ Best Practice, Cochrane Library, UptoDate) y en web de organismos oficiales en marzo de 2020, mediante descriptores y truncamientos. La búsqueda se limitó a revisiones publicadas entre 2016-2020. Resultados: Se identificaron 36 documentos (sin duplicados) de los que se seleccionaron, por pertinencia y especificidad 17, a los que se añadió un documento de la de lectura de la bibliografía. En los documentos finalmente utilizados, no se localizaron evidencias, pero sí experiencias y recomendaciones de interés, destacando la importancia de la desinfección del material, del ambiente y de manera muy significativa de las manos. Conclusión: No se aprecian claras evidencias, ni se identifican claras recomendaciones de usar uno u otro antiséptico, aunque se resalta la acción del hipoclorito de sodio, el etanol y el peróxido de hidrógeno frente a otros como el cloruro de benzalconio, el digluconato de clorhexidina, la povidona yodada y el alcohol étilico diluido. Especialmente se da importancia a utilizarlos en la higiene de manos, el uso de equipos de protección y de la desinfección del entorno. Abstract Objective: To synthesize the available evidence on the use of antiseptics and disinfectants in the face of VIDOC-19 infection Method: Bibliographic search in the main databases (WOS, CCC, DIIDW, KJD, MEDLINE, RSCI, SCIELO, PubMed, BMJ Best Practice, Cochrane Library, UptoDate) and on the web of official bodies in March 2020, using descriptors and truncations. The search was limited to reviews published between 2016-2020. Results: Thirty-six papers were identified (no duplicates) of which 17 were selected for relevance and specificity and one paper was added from the literature review. In the documents finally used, no evidence was located, but experiences and recommendations of interest were found, highlighting the importance of material, environmental and, very significantly, hand disinfection. Conclusion: There is no clear evidence, nor are there clear recommendations for the use of one or another antiseptic, although the action of sodium hypochlorite, ethanol and hydrogen peroxide is highlighted in comparison to others such as benzalkonium chloride, chlorhexidine digluconate, povidoeyodine and diluted ethyl alcohol. Particular importance is attached to their use in hand hygiene, the use of protective equipment and environmental disinfection.


title: Pulse immunosuppressive therapy for multiple sclerosis during the SARS-CoV-2 lockdown de-escalation plan: safety algorithm

text: Abstract Introduction The COVID-19 pandemic is changing approaches to diagnosis, treatment, and care provision in multiple sclerosis (MS). During both the initial and peak phases of the epidemic, the administration of disease-modifying drugs, typically immunosuppressants administered in pulses, was suspended due to the uncertainty about their impact on SARS-CoV-2 infection, mainly in contagious asymptomatic/presymptomatic patients. The purpose of this study is to present a safety algorithm enabling patients to resume pulse immunosuppressive therapy (PIT) during the easing of lockdown measures. Methods We developed a safety algorithm based on our clinical experience with MS and the available published evidence; the algorithm assists in the detection of contagious asymptomatic/presymptomatic cases and of patients with mild symptoms of SARS-CoV-2 infection with a view to withdrawing PIT in these patients and preventing new infections at day hospitals. Results We developed a clinical/microbiological screening algorithm consisting of a symptom checklist, applied during a teleconsultation 48 h before the scheduled session of PIT, and PCR testing for SARS-CoV-2 in nasopharyngeal exudate 24 h before the procedure. Conclusion The application of our safety algorithm presents a favourable risk-benefit ratio despite the fact that the actual proportion of asymptomatic and presymptomatic individuals is unknown. Systematic PCR testing, which provides the highest sensitivity for detecting presymptomatic cases, combined with early detection of symptoms of SARS-CoV-2 infection may reduce infections and improve detection of high-risk patients before they receive PIT.


title: Ambient Influenza and Avian Influenza Virus during Dust Storm Days and Background Days

text: BACKGROUND: The spread of influenza and highly pathogenic avian influenza (H5N1) presents a significant threat to human health. Avian influenza outbreaks in downwind areas of Asian dust storms (ADS) suggest that viruses might be transported by dust storms. OBJECTIVES: We developed a technique to measure ambient influenza and avian influenza viruses. We then used this technique to measure concentrations of these viruses on ADS days and background days, and to assess the relationships between ambient influenza and avian influenza viruses, and air pollutants. METHODS: A high-volume air sampler was used in parallel with a filter cassette to evaluate spiked samples and unspiked samples. Then, air samples were monitored during ADS seasons using a filter cassette coupled with a real-time quantitative polymerase chain reaction (qPCR) assay. Air samples were monitored during ADS season (1 January to 31 May 2006). RESULTS: We successfully quantified ambient influenza virus using the filtration/real-time qPCR method during ADS days and background days. To our knowledge, this is the first report describing the concentration of influenza virus in ambient air. In both the spiked and unspiked samples, the concentration of influenza virus sampled using the filter cassette was higher than that using the high-volume sampler. The concentration of ambient influenza A virus was significantly higher during the ADS days than during the background days. CONCLUSIONS: Our data imply the possibility of long-range transport of influenza virus.


docid: dphrrtzw

title: Infection and disease: cause and cure

text: Much can be learnt about the mechanisms by which micro‐organisms cause disease from the ways that they interact with cells and tissues. This issue of The Journal of Pathology contains articles that address the roles that cell and tissue biology and pathology are playing in the elucidation of these mechanisms. A review of variant Creutzfeldt–Jakob disease is followed by a discussion of severe acute respiratory syndrome (SARS). Two articles on human papillomavirus (HPV) infection address the association between viral infection and neoplasia, as do reviews on viruses and lymphoma/leukaemia, and Kaposi's sarcoma‐associated herpesvirus (human herpesvirus 8, HHV8). The section on viral disease concludes with an article on morbilliviruses. The intracellular effects of bacteria are addressed in a review of Listeria infection and a further review outlines recent advances in our knowledge of syphilis. Reviews on Helicobacter and gastric neoplasia, innate defences against methicillin‐resistant Staphylococcus aureus (MRSA) infection, and the function of granulomas in tuberculosis also address aspects of tissue responses to bacterial infection. Following a review of the function of immunoglobulin A in defence against infection, a group of articles considers vaccination and gene therapy approaches, the latter involving consideration of both viral and bacterial strategies. The reviews assembled here bridge several gaps: between microbiology and cellular pathology; between host and infecting organism; and between disease and therapy. It is clear that cell and tissue pathology approaches are of value in all of these spheres, providing cell and tissue relevance to microbiological and immunological observations. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


title: Protein based biomarkers for non-invasive Covid-19 detection

text: COVID-19 has become a substantial lethal disease worldwide, and early diagnosis is a significant concern for this virus. Currently, RT-PCR is being used worldwide for the detection of this virus with human to human transmission. Furthermore, the recent develop biosensor leading to others diagnosis approach but being invasive are painful and time taking. Another possibility can be protein-based biomarkers as an application of biosensors for detection and early diagnostics. Considering the other approach, that is, microfluidics-based biosensor, though being a non-invasive method, will be restricting virus transmission. This review commences with the recent develop biosensor for Covid-19 detection and listing down the available biomarkers with their secretion range comparison of normal to COVID-19 patients through clinical analysis in china and concludes with the future approach for the diagnosis.


title: Hemagglutinin activation of pathogenic avian influenza viruses of serotype H7 requires the protease recognition motif R-X-K/R-R

text: Abstract The hemagglutinin of influenza virus A/FPV/Rostock/34 (H7) was altered at its multibasic cleavage site by site-directed mutagenesis and assayed for proteolytic activation after expression in CV-1 cells. The results indicated that the cellular protease responsible for activation recognizes the tetrapeptide motif R-X-K/R-R that must be presented in the correct sequence position. Studies on plaque variants of influenza virus A/fowINictoria/75 (H7N7) showed that alteration of the consensus sequence resulted in a loss of pathogenicity for chickens.


In memoriam Thomas Ludwig Diepgen


title: An investigation of dairy calf management practices, colostrum quality, failure of transfer of passive immunity, and occurrence of enteropathogens among Australian dairy farms

text: ABSTRACT Calf preweaning morbidity and mortality risks have been reported as high in several countries, with average values approximating 35 and 7%, respectively. However, limited data are available for calf morbidity and mortality risks on Australian dairy farms. The aims of this study were (1) to investigate current calf management practices on dairy farms in Australia and their association with herd-level morbidity and mortality using a questionnaire-based, cross-sectional study; and (2) to estimate the prevalence of common enteropathogens causing diarrhea, the failure of passive transfer of immunity, and poor colostrum quality in a sample of Australian dairy farms. We analyzed 106 completed questionnaires and samples from 23 farms (202 fecal, 253 calf serum, and 221 colostrum samples). Morbidity and mortality risks reported by farmers in preweaned heifers were 23.8 and 5.6%, respectively. These risks were above the Australian dairy industry targets in 75.5 and 66.7% of respondents. The zoonotic pathogens Cryptosporidium spp. and Salmonella spp. were the most prevalent enteropathogens, with a true prevalence of 40.9 and 25.2%, respectively. Salmonella O-group D was present in 67.9% of Salmonella-positive samples, followed by O-groups B (17.9%) and C (10.7%). Failure of transfer of passive immunity (IgG <10 g/L) was observed in 41.9% of calves (mean herd-level prevalence of 36.2%), and only 19.5% of colostrum samples met the standards for immunoglobulin content and microbiological quality. Collectively, these data indicate that there is still considerable room for improvement in calf-rearing practices on Australian dairy farms, particularly with regard to colostrum management and feeding hygiene.


title: Current regulatory approaches for accessing potential COVID-19 therapies

text: This commentary aims to elaborate challenges in the regulatory approaches for accessing and investigating COVID-19 potential therapies either with off-label use, compassionate use, emergency use or for clinical trials. Since no therapies have been formally approved and completely effective and safe to date, the best clinical choice is acquired only after consistent and fair communication and collaboration between licensed clinicians, researchers, regulatory authorities, manufacturers and patients.


title: Differences in the tissue tropism to chicken oviduct epithelial cells between avian coronavirus IBV strains QX and B1648 are not related to the sialic acid binding properties of their spike proteins

text: The avian coronavirus (AvCoV) infectious bronchitis virus (IBV) is a major poultry pathogen. A characteristic feature of IBV is the occurrence of many different strains belonging to different serotypes, which makes a complete control of the disease by vaccinations a challenging task. Reasons for differences in the tissue tropism and pathogenicity between IBV strains, e.g. a predilection for the kidneys or the oviduct are still an open question. Strains of the QX genotype have been major pathogens in poultry flocks in Asia, Europe and other parts of the world. They are the cause of severe problems with kidney disease and reproductive tract disorders. We analysed infectivity and binding properties of the QX strain and compared them with those of the nephropathogenic strain B1648. As most IBV strains do not infect permanent cell lines and show infection only in primary chicken cells of the target organs, we developed a culture system for chicken oviduct explants. The epithelial cells of the oviduct showed a high susceptibility to infection by the QX strain and were almost resistant to infection by the nephropathogenic B1648 strain. Binding tests with isolated primary oviduct epithelial cells and soluble S1 proteins revealed that S1 proteins of two IBV strains bound with the same efficiency to oviduct epithelial cells. This attachment was sialic acid dependent, indicating that the sugar binding property of IBV spike proteins is not the limiting factor for differences in infection efficiency for the oviduct of the corresponding viruses.


title: Bumped kinase inhibitor 1369 is effective against Cystoisospora suis in vivo and in vitro

text: Cystoisosporosis is a leading diarrheal disease in suckling piglets. With the confirmation of resistance against the only available drug toltrazuril, there is a substantial need for novel therapeutics to combat the infection and its negative effects on animal health. In closely related apicomplexan species, bumped kinase inhibitors (BKIs) targeting calcium-dependent protein kinase 1 (CDPK1) were shown to be effective in inhibiting host-cell invasion and parasite growth. Therefore, the gene coding for Cystoisospora suis CDPK1 (CsCDPK1) was identified and cloned to investigate activity and thermal stabilization of the recombinant CsCDPK1 enzyme by BKI 1369. In this comprehensive study, the efficacy, safety and pharmacokinetics of BKI 1369 in piglets experimentally infected with Cystoisospora suis (toltrazuril-sensitive, Wien-I and toltrazuril-resistant, Holland-I strains) were determined in vivo and in vitro using an established animal infection model and cell culture, respectively. BKI 1369 inhibited merozoite proliferation in intestinal porcine epithelial cells-1 (IPEC-1) by at least 50% at a concentration of 40 nM, and proliferation was almost completely inhibited (>95%) at 200 nM. Nonetheless, exposure of infected cultures to 200 nM BKI 1369 for five days did not induce structural alterations in surviving merozoites as confirmed by transmission electron microscopy. Five-day treatment with BKI 1369 (10 mg/kg BW twice a day) effectively suppressed oocyst excretion and diarrhea and improved body weight gains in treated piglets without obvious side effects for both toltrazuril-sensitive, Wien-I and resistant, Holland-I C. suis strains. The plasma concentration of BKI 1369 in piglets increased to 11.7 μM during treatment, suggesting constant drug accumulation and exposure of parasites to the drug. Therefore, oral applications of BKI 1369 could potentially be a therapeutic alternative against porcine cystoisosporosis. For use in pigs, future studies on BKI 1369 should be directed towards ease of drug handling and minimizing treatment frequencies.


title: Technology innovations for food security in Singapore: A case study of future food systems for an increasingly natural resource-scarce world

text: BACKGROUND: Food security is becoming an increasingly important global issue. Anthropogenic factors such as rapid urbanization and industrialization have strained finite resources like land and water. Therefore, against the impending threat of food security, the world can no longer rely on traditional methods to meet its needs. Instead, more creative and technologically advanced methods must be adopted to maximise diminishing natural resources. Singapore is a good case study of a small city-state that is trying to increase its own self-production of food using technology. SCOPE AND APPROACH: This review highlights the technologies that Singapore have adopted in enhancing food security given its limitation in natural resources. These methodologies serve as a case study that can be used as a reference point in light of the increasingly finite natural resources. The review also presents the advantages of these techniques as well as challenges that need to be overcome for them to be more widely adopted. KEY FINDINGS AND CONCLUSION: To increase self-production of food and enhance its food security, Singapore has employed the use of technologies such as vertical farming and aquaponics in urban farming, nutrient recovery from food waste, biodegradable food packaging from durian rinds, natural preservatives, insect farming, microalgae and cultivated meat as alternative protein sources. These technologies workaround Singapore's land and natural resource constraints, which many countries around the world can adapt. However, many of them are still relatively nascent with numerous challenges, which have to be addressed before they can be widely accepted and implemented.


title: Neumonías bacterianas no neumocócicas (II). Infecciones respiratorias por Mycoplasma y Chlamydia. Neumonías víricas

text: Resumen Las neumonías no neumocócicas y víricas se incluyen en el grupo denominado neumonías atípicas. Son causadas por un amplio grupo de bacterias y virus, no obteniéndose en la mayoría de los casos el diagnóstico etiológico. Con frecuencia su presentación suele ser leve, aunque se han descrito casos fatales, principalmente en pacientes inmunocomprometidos. En ocasiones asocian clínica extrapulmonar dificultando su diagnóstico. Las pruebas microbiológicas no están indicadas en su diagnóstico, salvo en los casos de fracaso terapéutico o ante la necesidad de hospitalización del paciente. El tratamiento antibiótico empírico precoz debe iniciarse lo antes posible, puesto que esta medida ha demostrado disminuir la morbimortalidad. Las modificaciones en el mismo o la indicación de tratamiento antivírico asociado solo se realizan según la evolución clínica o la gravedad de la presentación. Otros tratamientos como la corticoterapia continúan siendo controvertidos. Abstract Non-pneumococcal and viral pneumonias are included in the group termed atypical pneumonias. They are caused by a wide range of bacteria and viruses; in most cases an aetiological diagnosis is not reached. Their clinical presentation is usually mild, although fatal cases have been described, principally in immunocompromised patients. Occasionally, extrapulmonary symptoms are associated, which makes diagnosis difficult. Microbiological tests are not indicated for diagnosis, except in the event of therapeutic failure or if the patient needs to be hospitalised. Early, empirical antibiotic treatment should be started as promptly as possible, since this has proven to reduce morbidity and mortality. Modifications to the treatment or associated viral treatment are only indicated according to the clinical progression or severity of the disease. Other treatments, such as corticotherapy, remain controversial.


title: Comparative studies of alignment, alignment-free and SVM based approaches for predicting the hosts of viruses based on viral sequences

text: Predicting the hosts of newly discovered viruses is important for pandemic surveillance of infectious diseases. We investigated the use of alignment-based and alignment-free methods and support vector machine using mononucleotide frequency and dinucleotide bias to predict the hosts of viruses, and applied these approaches to three datasets: rabies virus, coronavirus, and influenza A virus. For coronavirus, we used the spike gene sequences, while for rabies and influenza A viruses, we used the more conserved nucleoprotein gene sequences. We compared the three methods under different scenarios and showed that their performances are highly correlated with the variability of sequences and sample size. For conserved genes like the nucleoprotein gene, longer k-mers than mono- and dinucleotides are needed to better distinguish the sequences. We also showed that both alignment-based and alignment-free methods can accurately predict the hosts of viruses. When alignment is difficult to achieve or highly time-consuming, alignment-free methods can be a promising substitute to predict the hosts of new viruses.


title: Global Critical Care: Moving Forward in Resource-Limited Settings

text: Caring for critically ill patients is challenging in resource-limited settings, where the burden of disease and mortality from potentially treatable illnesses is higher than in resource-rich areas. Barriers to delivering quality critical care in these settings include lack of epidemiologic data and context-specific evidence for medical decision-making, deficiencies in health systems organization and resources, and institutional obstacles to implementation of life-saving interventions. Potential solutions include the development of common definitions for intensive care unit (ICU), intensivist, and intensive care to create a universal ICU organization framework; development of educational programs for capacity building of health care professionals working in resource-limited settings; global prioritization of epidemiologic and clinical research in resource-limited settings to conduct timely and ethical studies in response to emerging threats; adaptation of international guidelines to promote implementation of evidence-based care; and strengthening of health systems that integrates these interventions. This manuscript reviews the field of global critical care, barriers to safe high-quality care, and potential solutions to existing challenges. We also suggest a roadmap for improving the treatment of critically ill patients in resource-limited settings.


title: Synthetic modifications of the immunomodulating peptide thymopentin to confer anti-mycobacterial activity

text: Abstract Effective global control of tuberculosis (TB) is increasingly threatened by the convergence of multidrug-resistant TB and the human immunodeficiency virus (HIV) infection. TB/HIV coinfections exert a tremendous burden on the host's immune system, and this has prompted the clinical use of immunomodulators to enhance host defences as an alternative therapeutic strategy. In this study, we modified the clinically used synthetic immunomodulatory pentapeptide, thymopentin (TP-5, RKDVY), with six arginine residues (RR-6, RRRRRR) at the N- and C-termini to obtain the cationic peptides, RR-11 (RKDVYRRRRRR-NH2) and RY-11 (RRRRRRRKDVY-NH2), respectively. The arginine residues conferred anti-mycobacterial activity to TP-5 in the peptides as shown by effective minimum inhibitory concentrations of 125 mg/L and killing efficiencies of >99.99% against both rifampicin-susceptible and -resistant Mycobacterium smegmatis. The immunomodulatory action of the peptides remained unaffected as shown by their ability to stimulate TNF-α production in RAW 264.7 mouse macrophage cells. A distinct change in surface morphology after peptide treatment was observed in scanning electron micrographs, while confocal microscopy and dye leakage studies suggested bacterial membrane disruption by the modified peptides. The modified peptides were non-toxic and did not cause hemolysis of rat red blood cells up to a concentration of 2000 mg/L. Moreover, RY-11 showed synergism with rifampicin and reduced the effective concentration of rifampicin, while preventing the induction of rifampicin resistance. The synthetic peptides may have a potential application in both immunocompetent and immunocompromised TB patients.


title: Identification of one peptide which inhibited infectivity of avian infectious bronchitis virus in vitro

text: Purified avian infectious bronchitis virus (IBV) was used to screen a random phage display peptide library. After the fourth panning, 10 positive phages were sequenced and characterized. The phages specifically inhibited IBV infectivity in HeLa cells and blocked IBV haemagglutination. One linear peptide “GSH HRH VHS PFV” from the positive phages with the highest neutralization titer was synthesized and this peptide inhibited IBV infection in HeLa as well. The results may contribute to development of antiviral therapeutics for IBV and studying the determinants for viral and cell interaction.


title: Innovations in HIV-1 Vaccine Design

text: Abstract Purpose The field of HIV-1 vaccinology has evolved during the last 30 years from the first viral vector HIV gene insert constructs to vaccination regimens using a myriad of strategies. These strategies now include germline-targeting, lineage-based, and structure-guided immunogen design. This narrative review outlines the historical context of HIV vaccinology and subsequently highlights the scientific discoveries during the last 6 years that promise to propel the field forward. Methods We conducted a search of 2 electronic databases, PubMed and EMBASE, for experimental studies that involved new HIV immunogen designs between 2013 and 2019. During the title and abstract reviews, publications were excluded if they were written in language other than English and/or were a letter to the editor, a commentary, or a conference-only presentation. We then used ClinicalTrials.gov to identify completed and ongoing clinical trials using these strategies. Findings The HIV vaccinology field has undergone periods of significant growth during the last 3 decades. Findings elucidated in preclinical studies have revealed the importance of the interaction between the cellular and humoral immune system. As a result, several new rationally designed vaccine strategies have been developed and explored in the last 6 years, including native-like envelope trimers, nanoparticle, and mRNA vaccine design strategies among others. Several of these strategies have shown enough promise in animal models to progress toward first-in-human Phase I clinical trials. Implications Rapid developments in preclinical and early-phase clinical studies suggest that a tolerable and effective HIV vaccine may be on the horizon.


title: Seasonal and Pandemic A (H1N1) 2009 influenza vaccination coverage and attitudes among health-care workers in a Spanish University Hospital

text: Influenza vaccination coverage among health-care workers (HCWs) remains the lowest compared with other priority groups for immunization. Little is known about the acceptability and compliance with the pandemic (H1N1) 2009 influenza vaccine among HCWs during the current campaign. Between 23 December 2009 and 13 January 2010, once the workplace vaccination program was over, we conducted a cross-sectional, questionnaire-based survey at the University Hospital 12 de Octubre (Madrid, Spain). Five hundred twenty-seven HCWs were asked about their influenza immunization history during the 2009–2010 season, as well as the reasons for accepting or declining either the seasonal or pandemic vaccines. Multiple logistic-regression analysis was preformed to identify variables associated with immunization acceptance. A total of 262 HCWs (49.7%) reported having received the seasonal vaccine, while only 87 (16.5%) affirmed having received the pandemic influenza (H1N1) 2009 vaccine. “Self-protection” and “protection of the patient” were the most frequently adduced reasons for acceptance of the pandemic vaccination, whereas the existence of “doubts about vaccine efficacy” and “fear of adverse reactions” were the main arguments for refusal. Simultaneous receipt of the seasonal vaccine (odds ratio [OR]: 0.27; 95% confidence interval [95% CI]: 0.14–0.52) and being a staff (OR: 0.08; 95% CI: 0.04–0.19) or a resident physician (OR: 0.16; 95% CI: 0.05–0.50) emerged as independent predictors for pandemic vaccine acceptance, whereas self-reported membership of a priority group was associated with refusal (OR: 5.98; 95% CI: 1.35–26.5). The pandemic (H1N1) 2009 influenza vaccination coverage among the HCWs in our institution was very low (16.5%), suggesting the role of specific attitudinal barriers and misconceptions about immunization in a global pandemic scenario.


title: The pathogenesis of nephritis in chickens induced by infectious bronchitis virus

text: Abstract Nephritis in chickens caused by infectious bronchitis virus (IBV) was studied by virological, histological and electron microscopical methods. The T strain of the virus caused only mild respiratory signs in both Rhode Island Red (RIR) and White Leghorn (WL) breeds; the 50 per cent mortality induced was due to acute nephritis. All the infected birds developed high titres of antibody to IBV for up to 30 weeks. In spite of the persistence of antibody, about 35 per cent of the RIR developed chronic progressive nephritis. The histology showed varying degrees of pathological changes in the tubules, with relatively unaffected glomeruli. Foci of mononuclear cell infiltration were prominent in the cortex and medulla, particularly in chronic nephritis. Cytoplasmic IBV immunofluorescence was found in all segments of the tubules, but not in the glomeruli. There was no evidence of virus replication in the caecal tonsil and bursa of Fabricius. Evidence of extensive coronavirus replication was found in the cells of the tubules. A large number of viral inclusion bodies as seen containing dark smooth particles 120 nm in diameter within a single membrane. Virus was readily recovered from the kidneys as well as faeces of birds with acute and chronic nephritis. It is concluded that direct virus-induced cell lysis is the primary cause of IBV nephritis. In addition, about 50 per cent of the chronically infected birds also developed brush-border auto-antibody.


title: Collateral Damage of the COVID‐19 Pandemic on Nutritional Quality and Physical Activity: Perspective from South Korea

text: A novel coronavirus (SARS‐CoV‐2), that emerged in the city of Wuhan, China in December 2019, has now spread worldwide.


title: COVID‐19: Herd Immunity and Convalescent Plasma Transfer Therapy

text: Coronavirus disease 2019 (COVID‐19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2), has spread worldwide triggering a pandemic. Its first case was reported in Wuhan, the capital of China's Hubei province, and since then it has spread across world becoming one of the worst pandemics in the history of mankind(1). Its basic reproductive number (R(0)) has been determined to be 2‐3(2). This article is protected by copyright. All rights reserved.


title: The impact of COVID-19 as a necessary evil on air pollution in India during the lockdown()

text: The study objective is to contemplate the effectiveness of COVID-19 on the air pollution of Indian territory from January 2020 to April 2020. We have executed data from European Space Agency (ESA) and CPCB online portal for air quality data dissemination. The Sentinel – 5 P satellite images elucidate that the Air quality of Indian territory has been improved significantly during COVID-19. Mumbai and Delhi are one of the most populated cities. These two cities have observed a substantial decrease in Nitrogen Dioxide (40–50%) compared to the same period last year. It suggests that the emergence of COVID-19 has been proved to a necessary evil as being advantageous for mitigating air pollution on Indian territory during the lock-down. The study found a significant decline in Nitrogen Dioxide in reputed states of India, i.e., Delhi and Mumbai. Moreover, a faded track of Nitrogen Dioxide can be seen at the Maritime route in the Indian Ocean. An upsurge in the environmental quality of India will also be beneficial for its neighbor countries, i.e., China, Pakistan, Iran, and Afghanistan.