title: Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition

text: It is well understood that the adaptive immune response to infectious agents includes a modulating suppressive component as well as an activating component. We now show that the very early innate response also has an immunosuppressive component. Infected cells upregulate the CD47 “don’t eat me” signal, which slows the phagocytic uptake of dying and viable cells as well as downstream antigen-presenting cell (APC) functions. A CD47 mimic that acts as an essential virulence factor is encoded by all poxviruses, but CD47 expression on infected cells was found to be upregulated even by pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that encode no mimic. CD47 upregulation was revealed to be a host response induced by the stimulation of both endosomal and cytosolic pathogen recognition receptors (PRRs). Furthermore, proinflammatory cytokines, including those found in the plasma of hepatitis C patients, upregulated CD47 on uninfected dendritic cells, thereby linking innate modulation with downstream adaptive immune responses. Indeed, results from antibody-mediated CD47 blockade experiments as well as CD47 knockout mice revealed an immunosuppressive role for CD47 during infections with lymphocytic choriomeningitis virus and Mycobacterium tuberculosis. Since CD47 blockade operates at the level of pattern recognition receptors rather than at a pathogen or antigen-specific level, these findings identify CD47 as a novel potential immunotherapeutic target for the enhancement of immune responses to a broad range of infectious agents.


title: Lung function and bronchial hyper‐responsiveness 11 years after hospitalization for bronchiolitis

text: Aim: Atopic infants hospitalized for wheezing not caused by respiratory syncytial virus (RSV) carry the highest risk for later asthma. In the present paper, early risk factors for later lung function abnormalities and for bronchial hyper‐responsiveness (BHR) were evaluated in 81 children, hospitalized for bronchiolitis in infancy, at the median age of 12.3 years. Methods: The basic data, including data on atopy in children and viral aetiology of bronchiolitis, had been collected on entry to the study at less than 2 years of age. Lung function was studied by flow‐volume spirometry (FVS), and BHR by methacholine and exercise challenge tests 11.4 years after hospitalization during infancy. Results: RSV aetiology of bronchiolitis was associated with reduced forced vital capacity (FVC; 93.65% of predicted ± 11.05 vs. 99.57%± 12.59, p = 0.009). Early sensitization to inhalant allergens (OR 12.59, 95% CI 2.30–68.77) and maternal smoking during pregnancy (OR 4.58, 95% CI 1.28–16.39) were associated with BHR to exercise, and early atopic dermatitis (OR 3.48, 95% CI 1.09–11.10) was associated with BHR to methacholine. Conclusions: RSV bronchiolitis was associated with a restrictive pattern of lung function. Early atopy and maternal smoking during pregnancy may play a role in the development and persistence of BHR.


title: Laboratory Changes Consistent with Feline Infectious Peritonitis in Cats from Multicat Environments

text: The present study describes the prevalence of haematological and electrophoretic changes consistent with the diagnosis of feline infectious peritonitis (FIP) in cats without FIP living in six multicat environments with different prevalence of FIP and of other diseases. The results allow designing haematological and electrophoretic profiles typical of each group, most likely depending on the management and on the health status of the group rather than on the prevalence of FIP. In fact, many cats from the colonies with open management and frequent outbreaks of infectious diseases other than FIP had one or more haematological and/or electrophoretical changes consistent with FIP, compared with the reference ranges. In the case of non‐specific clinical signs such as fever or neurological signs because of diseases other than FIP, these cats would be erroneously considered as affected by FIP and euthanasized. The use of internal ranges designed on the basis of repeated samplings from non‐symptomatic cats allows avoiding these misinterpretations. Results from cats with symptoms consistent with FIP living in the same colonies were also compared with both the reference ranges and the internal ones: such a comparison demonstrated that the use of internal ranges rarely affected the possibility to correctly diagnose the disease in cats with symptoms suggestive of FIP.


title: When time drags

text: The coronavirus pandemic is making life feel very slow, but observing timescales across the universe can bring us some comfort, writes Chanda Prescod-Weinstein


title: Understanding Fc Receptor Involvement in Inflammatory Diseases: From Mechanisms to New Therapeutic Tools

text: Fc receptors (FcRs) belong to the ITAM-associated receptor family. FcRs control the humoral and innate immunity which are essential for appropriate responses to infections and prevention of chronic inflammation or auto-immune diseases. Following their crosslinking by immune complexes, FcRs play various roles such as modulation of the immune response by released cytokines or of phagocytosis. Here, we review FcR involvement in pathologies leading notably to altered intracellular signaling with functionally relevant consequences to the host, and targeting of Fc receptors as therapeutic approaches. Special emphasis will be given to some FcRs, such as the FcαRI, the FcγRIIA and the FcγRIIIA, which behave like the ancient god Janus depending on the ITAM motif to inhibit or activate immune responses depending on their targeting by monomeric/dimeric immunoglobulins or by immune complexes. This ITAM duality has been recently defined as inhibitory or activating ITAM (ITAMi or ITAMa) which are controlled by Src family kinases. Involvement of various ITAM-bearing FcRs observed during infectious or autoimmune diseases is associated with allelic variants, changes in ligand binding ability responsible for host defense perturbation. During auto-immune diseases such as rheumatoid arthritis, lupus or immune thrombocytopenia, the autoantibodies and immune complexes lead to inflammation through FcR aggregation. We will discuss the role of FcRs in autoimmune diseases, and focus on novel approaches to target FcRs for resolution of antibody-mediated autoimmunity. We will finally also discuss the down-regulation of FcR functionality as a therapeutic approach for autoimmune diseases.


title: Risk Factors for SARS among Persons without Known Contact with SARS Patients, Beijing, China

text: Most cases of severe acute respiratory syndrome (SARS) have occurred in close contacts of SARS patients. However, in Beijing, a large proportion of SARS cases occurred in persons without such contact. We conducted a case-control study in Beijing that compared exposures of 94 unlinked, probable SARS patients with those of 281 community-based controls matched for age group and sex. Case-patients were more likely than controls to have chronic medical conditions or to have visited fever clinics (clinics at which possible SARS patients were separated from other patients), eaten outside the home, or taken taxis frequently. The use of masks was strongly protective. Among 31 case-patients for whom convalescent-phase (>21 days) sera were available, 26% had immunoglobulin G to SARS-associated coronavirus. Our finding that clinical SARS was associated with visits to fever clinics supports Beijing’s strategy of closing clinics with poor infection-control measures. Our finding that mask use lowered the risk for disease supports the community’s use of this strategy.


docid: amzmyqys

title: Potential targets for anti-SARS drugs in the structural proteins from SARS related coronavirus

text: This is a further study on the severe acute respiratory syndrome (SARS) using the probabilistic models. The purpose was to define the potential targets for anti-SARS drugs in the structural proteins from human SARS related coronavirus (SARS-CoV) while knowing little about the functional sites and possible mutations in these proteins. From a probabilistic viewpoint, we can theoretically select the amino acid pairs as potential candidates for anti-SARS drugs. These candidates have a greater chance of colliding with anti-SARS drugs, are more likely to link with the protein functions and are less vulnerable to mutations.


title: Overexpression of fibrinogen-like protein 2 induces epithelial-to-mesenchymal transition and promotes tumor progression in colorectal carcinoma

text: The main cause of death in colorectal carcinoma (CRC) patients is tumor metastasis; however, the underlying molecular mechanisms are largely unknown. In the present study, a novel metastasis-related gene, fibrinogen-like protein 2 (FGL2), was characterized for its role in CRC metastasis and underlying molecular mechanisms. The clinical significance of FGL2 was investigated using tissue microarray analysis of samples from 82 patients with CRC. The molecular effects of FGL2 in CRC cells were determined using RNA interference and ectopic expression of FGL2. The overexpression of FGL2 was examined by immunohistochemistry in 82 CRC patients, and it was determined to be an independent predictor of overall survival (P < 0.05). The depletion of FGL2 expression inhibited tumor progression and epithelial-to-mesenchymal transition (EMT) in vitro and in vivo, while ectopic overexpression of FGL2 enhanced cell invasion and induced EMT in vitro. Our results suggest that FGL2 plays an important oncogenic role in CRC aggressiveness by inducing EMT, and FGL2 could be employed as a novel prognostic marker and effective therapeutic target for CRC.


title: Analysis for fractional dynamics of Ebola virus model

text: Ebola virus is very challenging problem of the world. The main purpose of this work is to study fractional Ebola virus model. An efficient computational method based on iterative scheme is proposed to solve fractional Ebola model numerically. Stability of proposed method is also discussed. Efficiency of proposed method is shown by listing CPU time. Proposed computational method will work for long time domain. Numerical results are presented graphically. The main reason for using this technique is low computational cost and high accuracy. It is also shown how the approximate solution varies for fractional and integer order Ebola virus model.


title: Coronavirus lockdown helped the environment to bounce back

text: As the transmission of novel corona virus (COVID-19) increases rapidly, the whole world adopted the curfew/lockdown activity with restriction of human mobility. The imposition of quarantine stopped all the commercial activity that greatly affects the various important environmental parameters which directly connected to human health. As all the types of social, economic, industrial and urbanization activity suddenly shut off, nature takes the advantages and showed improvement in the quality of air, cleaner rivers, less noise pollution, undisturbed and calm wildlife. This research aims to discuss the COVID-19 effect on the global environment. The outcome of this research says that “Although coronavirus vaccine is not available coronavirus itself is earth's vaccine and us humans are the virus”.


docid: swribqwr

title: COVID-19: Fear, quackery, false representations and the law()

text: Fear, anxiety and even paranoia can proliferate during a pandemic. Such conditions, even when subclinical, tend to be a product of personal and predispositional factors, as well as shared cultural influences, including religious, literary, film, and gaming, all of which can lead to emotional and less than rational responses. They can render people vulnerable to engage in implausible conspiracy theories about the causes of illness and governmental responses to it. They can also lead people to give credence to simplistic and unscientific misrepresentations about medications and devices which are claimed to prevent, treat or cure disease. In turn such vulnerability creates predatory opportunities for the unscrupulous. This article notes the eruption of quackery during the 1889–1892 Russian Flu and the 1918–1920 Spanish Flu and the emergence during 2020 of spurious claims during the COVID-19 pandemic. It identifies consumer protection strategies and interventions formulated during the 2020 pandemic. Using examples from the United States, Japan, Australia and the United Kingdom, it argues that during a pandemic there is a need for three responses by government to the risks posed by conspiracy theories and false representations: calm, scientifically-based messaging from public health authorities; cease and desist warnings directed toward those making extravagant or inappropriate claims; and the taking of assertive and well publicised legal action against individuals and entities that make false representations during a pandemic in order to protect consumers rendered vulnerable by their emotional responses to the phenomenology of the pandemic.


Income security in times of ill health: the next frontier for the SDGs


docid: hzvuzqca

title: Collaborative Care at a Distance: Student Therapists' Experiences of Learning and Delivering Relationally Focused Telemental Health

text: There is mounting evidence that telemental health is an effective delivery method for treating a variety of mental, emotional, behavioral, and relational health problems. While many of the therapeutic skills leading to the effectiveness of face‐to‐face treatments are transferable, the effectiveness of telemental health requires unique skills. The purpose of this phenomenological study was to determine the experience of learning how to use videoconferencing to deliver relationally focused mental health care. Participants included 10 graduates of a COAMFTE‐accredited master's degree program emphasizing training in telemental health. Each student had practicum placements that required videoconferencing to deliver relationally based psychotherapy. Analysis of interview data revealed (a) personal reservations about distance delivery; (b) the importance of scaffolding student learning through curriculum, supervision, and mental health‐care delivery protocols; (c) the technological barriers associated with this delivery method; and (d) overcoming technological barriers through intentionality.


title: Identification of diverse full-length endogenous betaretroviruses in megabats and microbats

text: BACKGROUND: Betaretroviruses infect a wide range of species including primates, rodents, ruminants, and marsupials. They exist in both endogenous and exogenous forms and are implicated in animal diseases such as lung cancer in sheep, and in human disease, with members of the human endogenous retrovirus-K (HERV-K) group of endogenous betaretroviruses (βERVs) associated with human cancers and autoimmune diseases. To improve our understanding of betaretroviruses in an evolutionarily distinct host species, we characterized βERVs present in the genomes and transcriptomes of mega- and microbats, which are an important reservoir of emerging viruses. RESULTS: A diverse range of full-length βERVs were discovered in mega- and microbat genomes and transcriptomes including the first identified intact endogenous retrovirus in a bat. Our analysis revealed that the genus Betaretrovirus can be divided into eight distinct sub-groups with evidence of cross-species transmission. Betaretroviruses are revealed to be a complex retrovirus group, within which one sub-group has evolved from complex to simple genomic organization through the acquisition of an env gene from the genus Gammaretrovirus. Molecular dating suggests that bats have contended with betaretroviral infections for over 30 million years. CONCLUSIONS: Our study reveals that a diverse range of betaretroviruses have circulated in bats for most of their evolutionary history, and cluster with extant betaretroviruses of divergent mammalian lineages suggesting that their distribution may be largely unrestricted by host species barriers. The presence of βERVs with the ability to transcribe active viral elements in a major animal reservoir for viral pathogens has potential implications for public health.


title: Advances in nanomaterials and their applications in point of care (POC) devices for the diagnosis of infectious diseases

text: Abstract Nanotechnology has gained much attention over the last decades, as it offers unique opportunities for the advancement of the next generation of sensing tools. Point-of-care (POC) devices for the selective detection of biomolecules using engineered nanoparticles have become a main research thrust in the diagnostic field. This review presents an overview on how the POC-associated nanotechnology, currently applied for the identification of nucleic acids, proteins and antibodies, might be further exploited for the detection of infectious pathogens: although still premature, future integrations of nanoparticles with biological markers that target specific microorganisms will enable timely therapeutic intervention against life-threatening infectious diseases.


Quels enjeux de nature Ethique l’épidémie de COVID 19 a-t-elle soulevé?


title: Persistent infections support maintenance of a coronavirus in a population of Australian bats (Myotis macropus)

text: Understanding viral transmission dynamics within populations of reservoir hosts can facilitate greater knowledge of the spillover of emerging infectious diseases. While bat-borne viruses are of concern to public health, investigations into their dynamics have been limited by a lack of longitudinal data from individual bats. Here, we examine capture–mark–recapture (CMR) data from a species of Australian bat (Myotis macropus) infected with a putative novel Alphacoronavirus within a Bayesian framework. Then, we developed epidemic models to estimate the effect of persistently infectious individuals (which shed viruses for extensive periods) on the probability of viral maintenance within the study population. We found that the CMR data analysis supported grouping of infectious bats into persistently and transiently infectious bats. Maintenance of coronavirus within the study population was more likely in an epidemic model that included both persistently and transiently infectious bats, compared with the epidemic model with non-grouping of bats. These findings, using rare CMR data from longitudinal samples of individual bats, increase our understanding of transmission dynamics of bat viral infectious diseases.


title: Digital Contact Tracing, Privacy, and Public Health

text: Digital contact tracing, in combination with widespread testing, has been a focal point for many plans to “reopen” economies while containing the spread of Covid‐19. Most digital contact tracing projects in the United States and Europe have prioritized privacy protections in the form of local storage of data on smartphones and the deidentification of information. However, in the prioritization of privacy in this narrow form, there is not sufficient attention given to weighing ethical trade‐offs within the context of a public health pandemic or to the need to evaluate safety and effectiveness of software‐based technology applied to public health.


title: Mammalian microRNA: an important modulator of host-pathogen interactions in human viral infections

text: MicroRNAs (miRNAs), which are small non-coding RNAs expressed by almost all metazoans, have key roles in the regulation of cell differentiation, organism development and gene expression. Thousands of miRNAs regulating approximately 60 % of the total human genome have been identified. They regulate genetic expression either by direct cleavage or by translational repression of the target mRNAs recognized through partial complementary base pairing. The active and functional unit of miRNA is its complex with Argonaute proteins known as the microRNA-induced silencing complex (miRISC). De-regulated miRNA expression in the human cell may contribute to a diverse group of disorders including cancer, cardiovascular dysfunctions, liver damage, immunological dysfunction, metabolic syndromes and pathogenic infections. Current day studies have revealed that miRNAs are indeed a pivotal component of host-pathogen interactions and host immune responses toward microorganisms. miRNA is emerging as a tool for genetic study, therapeutic development and diagnosis for human pathogenic infections caused by viruses, bacteria, parasites and fungi. Many pathogens can exploit the host miRNA system for their own benefit such as surviving inside the host cell, replication, pathogenesis and bypassing some host immune barriers, while some express pathogen-encoded miRNA inside the host contributing to their replication, survival and/or latency. In this review, we discuss the role and significance of miRNA in relation to some pathogenic viruses.


title: A new role of neuraminidase (NA) in the influenza virus life cycle: implication for developing NA inhibitors with novel mechanism of action

text: The entire life cycle of influenza virus involves viral attachment, entry, replication, and release. Previous studies have demonstrated that neuraminidase (NA) is an essential glycoprotein on the surface of influenza virus and that it is responsible for release of progeny virions from the host cell to infect new cells. However, recent studies have also suggested that NA may play other roles in the early stages of the viral life cycle, that is, viral attachment and entry. This review focuses on the new role of NA in the early stages of influenza life cycle and the corresponding development of novel NA inhibitors. Copyright © 2016 John Wiley & Sons, Ltd.


title: Three-Dimensional Analysis of a Viral RNA Replication Complex Reveals a Virus-Induced Mini-Organelle

text: Positive-strand RNA viruses are the largest genetic class of viruses and include many serious human pathogens. All positive-strand RNA viruses replicate their genomes in association with intracellular membrane rearrangements such as single- or double-membrane vesicles. However, the exact sites of RNA synthesis and crucial topological relationships between relevant membranes, vesicle interiors, surrounding lumens, and cytoplasm generally are poorly defined. We applied electron microscope tomography and complementary approaches to flock house virus (FHV)–infected Drosophila cells to provide the first 3-D analysis of such replication complexes. The sole FHV RNA replication factor, protein A, and FHV-specific 5-bromouridine 5'-triphosphate incorporation localized between inner and outer mitochondrial membranes inside ∼50-nm vesicles (spherules), which thus are FHV-induced compartments for viral RNA synthesis. All such FHV spherules were outer mitochondrial membrane invaginations with interiors connected to the cytoplasm by a necked channel of ∼10-nm diameter, which is sufficient for ribonucleotide import and product RNA export. Tomographic, biochemical, and other results imply that FHV spherules contain, on average, three RNA replication intermediates and an interior shell of ∼100 membrane-spanning, self-interacting protein As. The results identify spherules as the site of protein A and nascent RNA accumulation and define spherule topology, dimensions, and stoichiometry to reveal the nature and many details of the organization and function of the FHV RNA replication complex. The resulting insights appear relevant to many other positive-strand RNA viruses and support recently proposed structural and likely evolutionary parallels with retrovirus and double-stranded RNA virus virions.


title: The pathogens profile in children with otitis media with effusion and adenoid hypertrophy

text: OBJECTIVES: To evaluate the presence of viruses and bacteria in middle ear and adenoids of patients with and without otitis media with effusion (OME). METHODS: Adenoid samples and middle ear washes (MEW) were obtained from children with OME associated with adenoid hypertrophy undergoing adenoidectomy and tympanostomy, and compared to those obtained from patients undergoing cochlear implant surgery, as a control group. Specific DNA or RNA of 9 respiratory viruses (rhinovirus, influenza virus, picornavirus, syncytial respiratory virus, metapneumovirus, coronavirus, enterovirus, adenovirus and bocavirus) and 5 bacteria (S. pneumoniae, H. influenzae, M. catarrhalis, P. aeruginosa and S. aureus) were extracted and quantified by real-time PCR. RESULTS: 37 OME and 14 cochlear implant children were included in the study. At the adenoid, virus and bacteria were similarly detected in both OME and control patients. At the middle ear washes, however, a higher prevalence of bacteria was observed in patients with OME (p = 0.01). S. pneumoniae (p = 0.01) and M. catarrhalis (p = 0.022) were the bacteria responsible for this difference. Although total virus detection was not statistically different from controls at the middle ear washes (p = 0.065), adenovirus was detected in higher proportions in adenoid samples of OME patients than controls (p = 0.019). CONCLUSIONS: Despite both OME and control patients presented similar rates of viruses and bacteria at the adenoid, children with OME presented higher prevalence of S. pneumonia, M. catarrhalis in middle ear and adenovirus in adenoids when compared to controls. These findings could suggest that these pathogens could contribute to the fluid persistence in the middle ear.


title: The Correlation of Comorbidities on the Mortality in Patients with COVID-19: an Observational Study Based on the Korean National Health Insurance Big Data

text: BACKGROUND: Mortality of coronavirus disease 2019 (COVID-19) is a major concern for quarantine departments in all countries. This is because the mortality of infectious diseases determines the basic policy stance of measures to prevent infectious diseases. Early screening of high-risk groups and taking action are the basics of disease management. This study examined the correlation of comorbidities on the mortality of patients with COVID-19. METHODS: We constructed epidemiologic characteristics and medical history database based on the Korean National Health Insurance Service Big Data and linked COVID-19 registry data of Korea Centers for Disease Control & Prevention (KCDC) for this emergent observational cohort study. A total of 9,148 patients with confirmed COVID-19 were included. Mortalities by sex, age, district, income level and all range of comorbidities classified by International Classification of Diseases-10 based 298 categories were estimated. RESULTS: There were 3,556 male confirmed cases, 67 deaths, and crude death rate (CDR) of 1.88%. There were 5,592 females, 63 deaths, and CDR of 1.13%. The most confirmed cases were 1,352 patients between the ages of 20 to 24, followed by 25 to 29. As a result of multivariate logistic regression analysis that adjusted epidemiologic factors to view the risk of death, the odds ratio of death would be hemorrhagic conditions and other diseases of blood and blood-forming organs 3.88-fold (95% confidence interval [CI], 1.52–9.88), heart failure 3.17-fold (95% CI, 1.88–5.34), renal failure 3.07-fold (95% CI, 1.43–6.61), prostate malignant neoplasm 2.88-fold (95% CI, 1.01–8.22), acute myocardial infarction 2.38-fold (95% CI, 1.03–5.49), diabetes was 1.82-fold (95% CI, 1.25–2.67), and other ischemic heart disease 1.71-fold (95% CI, 1.09–2.66). CONCLUSION: We hope that this study could provide information on high risk groups for preemptive interventions. In the future, if a vaccine for COVID-19 is developed, it is expected that this study will be the basic data for recommending immunization by selecting those with chronic disease that had high risk of death, as recommended target diseases for vaccination.


title: Critical evaluation of FDA-approved respiratory multiplex assays for public health surveillance

text: Introduction: Clinical management and identification of respiratory diseases has become more rapid and increasingly specific due to widespread use of PCR(polymerase chain reaction) multiplex technologies. Although significantly improving clinical diagnosis, multiplexed PCR assays could have a greater impact on local and global disease surveillance. The authors wish to propose methods of evaluating respiratory multiplex assays to maximize diagnostic yields specifically for surveillance efforts. Areas covered: The authors review multiplexed assays and critically assess what barriers have limited these assays for disease surveillance and how these barriers might be addressed. The manuscript focuses specifically on the case study of using multiplexed assays for surveillance of respiratory pathogens. The authors also provide a method of validation of specific surveillance measures. Expert commentary: Current commercially available respiratory multiplex PCR assays are widely used for clinical diagnosis; however, specific barriers have limited their use for surveillance. Key barriers include differences in testing phase requirements and diagnostic performance evaluation. In this work the authors clarify phase testing requirements and introduce unique diagnostic performance measures that simplify the use of these assays on a per target basis for disease surveillance.


title: Characterization of viral proteins encoded by the SARS-coronavirus genome

text: Abstract A new disease, termed severe acute respiratory syndrome (SARS), emerged at the end of 2002 and caused profound disturbances in over 30 countries worldwide in 2003. A novel coronavirus was identified as the aetiological agent of SARS and the 30kb viral genome was deciphered with unprecedented speed in a coordinated manner by the global community. Since then, much progress has been made in the virological and molecular characterization of the proteins encoded by SARS-coronavirus (SARS-CoV) genome, which contains 14 potential open reading frames (ORFs). These investigations can be broadly classified into three groups: (a) studies on the replicase 1a/1b gene products which are important for viral replication, (b) studies on the structural proteins, spike, nucleocapsid, membrane and envelope, which have homologues in all coronaviruses, and are important for viral assembly and (c) expression and functional studies of the “accessory” proteins that are specifically encoded by SARS-CoV. A comparison of the properties of these three groups of SARS-CoV proteins with the knowledge that coronavirologists have generated over more than 30 years of research can help us in the prevention and treatment of SARS in the event of the re-emergence of this new infectious disease.


title: Three-dimensional tumor cell cultures employed in virotherapy research

text: Oncolytic virotherapy constitutes an upcoming alternative treatment option for a broad spectrum of cancer entities. However, despite great research efforts, there is still only a single US Food and Drug Administration/European Medicines Agency-approved oncolytic virus available for clinical use. One reason for that is the gap between promising preclinical data and limited clinical success. Since oncolytic viruses are biological agents, they might require more realistic in vitro tumor models than common monolayer tumor cell cultures to provide meaningful predictive preclinical evaluation results. For more realistic invitro tumor models, three-dimensional tumor cell-culture systems can be employed in preclinical virotherapy research. This review provides an overview of spheroid and hydrogel tumor cell cultures, organotypic tumor-tissue slices, organotypic raft cultures, and tumor organoids utilized in the context of oncolytic virotherapy. Furthermore, we also discuss advantages, disadvantages, techniques, and difficulties of these three-dimensional tumor cell-culture systems when applied specifically in virotherapy research.


title: An Outbreak Preparedness and Mitigation Approach in Home Health and Personal Home Care During the COVID-19 Pandemic

text: The acute respiratory disease COVID-19, caused by the novel Coronavirus SARS-CoV-2, is a worldwide pandemic affecting millions of people. The methodology that organizations who provide home health and personal home care services are using to respond to this pandemic has not yet been characterized. In this report, we describe our approach to comprehensive outbreak suppression and report an initial case series of COVID-19 positive patients receiving home-based services. We implemented enhanced infection control procedures across our affiliates, and we communicated these protocols to our offices using multi-faceted methods. Using custom built software applications enabling us to track patient and employee cases and exposures, we leveraged current public health recommendations to identify cases and to suppress transmission. In the 100-day period between January 20, 2020 and April 30, 2020, our affiliates provided services to 67 COVID-19 positive patients (<0.3% of census). Twenty patients were referred to home health post hospitalization for COVID-19 related illness, whereas 47 were found to have COVID-19 while living in community settings. Of those who were found to have COVID-19 in the community, 17 (39%) required subsequent hospitalization. Hospitalized patients had an average age of 74.5 ± 18, and 53% were male. There were 13 deaths (76%) among those hospitalized from the community with COVID-19 related illness. A highly coordinated and frequently communicated approach to infection control, case identification and employee screening can be performed by home health and personal home care organizations. Studies that further assess risks and predictors of illness severity in home-based COVID-19 patients are needed.


title: Peptide domains involved in the localization of the porcine reproductive and respiratory syndrome virus nucleocapsid protein to the nucleolus

text: Abstract The nucleocapsid (N) protein of porcine reproductive and respiratory syndrome virus (PRRSV) is the principal component of the viral nucleocapsid and localizes to the nucleolus. Peptide sequence analysis of the N protein of several North American isolates identified two potential nuclear localization signal (NLS) sequences located at amino acids 10–13 and 41–42, which were labeled NLS-1 and NLS-2, respectively. Peptides containing NLS-1 or NLS-2 were sufficient to accumulate enhanced green fluorescent protein (EGFP) in the nucleus. The inactivation of NLS-1 by site-directed mutagenesis or the deletion of the first 14 amino acids did not affect N protein localization to the nucleolus. The substitution of key lysine residues with uncharged amino acids in NLS-2 blocked nuclear/nucleolar localization. Site-directed mutagenesis within NLS-2 identified the sequence, KKNKK, as forming the core localization domain within NLS-2. Using an in vitro pull-down assay, the N protein was able to bind importin-α, importin-β nuclear transport proteins. The localization pattern of N-EGFP fusion peptides represented by a series of deletions from the C- and N-terminal ends of the N protein identified a region covering amino acids 41–72, which contained a nucleolar localization signal (NoLS) sequence. The 41–72 N peptide when fused to EGFP mimicked the nucleolar–cytoplasmic distribution of native N. These results identify a single NLS involved in the transport of N from the cytoplasm and into nucleus. An additional peptide sequence, overlapping NLS-2, is involved in the further targeting of N to the nucleolus.


title: Enteric Viruses☆

text: Abstract Many viruses use the enteric tract as a route of entry to the human, animal or avian host. The onset of acute enteritis is associated with infection by viruses that replicate at or near the site of entry into the intestinal mucosa, including caliciviruses, rotaviruses, adenoviruses, astroviruses, and coronaviruses. These ‘enteric’ viruses occur globally and share similar features. Most are RNA viruses that replicate in the cytoplasm of mature absorptive epithelial cells lining the villi of the small intestine, leading to inflammation and villus atrophy. Vomiting and diarrhea can result in dehydration and death if untreated. Despite abundant growth in vivo, they initially proved difficult or impossible to grow in vitro. Most are genetically diverse, species specific, highly infectious within species and transmitted by the fecal-oral route. Severe symptoms are most commonly associated with primary infections of young animals, and are followed by short-lived immunity. Reinfections are common throughout life, but are often only mildly symptomatic. Safe and effective vaccines have been developed to prevent severe rotavirus disease in young children. In addition to these enterotropic viruses, enteric disease can also result from spread to the intestine of HIV or cytomegaloviruses during the later stages of systemic disease in immunocompromised hosts.


title: Software for optimization of SNP and PCR-RFLP genotyping to discriminate many genomes with the fewest assays

text: BACKGROUND: Microbial forensics is important in tracking the source of a pathogen, whether the disease is a naturally occurring outbreak or part of a criminal investigation. RESULTS: A method and SPR Opt (SNP and PCR-RFLP Optimization) software to perform a comprehensive, whole-genome analysis to forensically discriminate multiple sequences is presented. Tools for the optimization of forensic typing using Single Nucleotide Polymorphism (SNP) and PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) analyses across multiple isolate sequences of a species are described. The PCR-RFLP analysis includes prediction and selection of optimal primers and restriction enzymes to enable maximum isolate discrimination based on sequence information. SPR Opt calculates all SNP or PCR-RFLP variations present in the sequences, groups them into haplotypes according to their co-segregation across those sequences, and performs combinatoric analyses to determine which sets of haplotypes provide maximal discrimination among all the input sequences. Those set combinations requiring that membership in the fewest haplotypes be queried (i.e. the fewest assays be performed) are found. These analyses highlight variable regions based on existing sequence data. These markers may be heterogeneous among unsequenced isolates as well, and thus may be useful for characterizing the relationships among unsequenced as well as sequenced isolates. The predictions are multi-locus. Analyses of mumps and SARS viruses are summarized. Phylogenetic trees created based on SNPs, PCR-RFLPs, and full genomes are compared for SARS virus, illustrating that purported phylogenies based only on SNP or PCR-RFLP variations do not match those based on multiple sequence alignment of the full genomes. CONCLUSION: This is the first software to optimize the selection of forensic markers to maximize information gained from the fewest assays, accepting whole or partial genome sequence data as input. As more sequence data becomes available for multiple strains and isolates of a species, automated, computational approaches such as those described here will be essential to make sense of large amounts of information, and to guide and optimize efforts in the laboratory. The software and source code for SPR Opt is publicly available and free for non-profit use at .


title: An agent-based model to evaluate the COVID-19 transmission risks in facilities

text: The rapid spread of the coronavirus disease (COVID-19) has become a global threat affecting almost all countries in the world. As countries reach the infection peak, it is planned to return a new normal under different coexistence conditions in order to reduce the economic effects produced by the total or partial closure of companies, universities, shops, etc. Under such circumstances, the use of mathematical models to evaluate the transmission risk of COVID-19 in various facilities represents an important tool in assisting authorities to make informed decisions. On the other hand, agent-based modeling is a relatively new approach to model complex systems composed of agents whose behavior is described using simple rules. Different from classical mathematical models (which consider a homogenous population), agent-based approaches model individuals with distinct characteristics and provide more realistic results. In this paper, an agent-based model to evaluate the COVID-19 transmission risks in facilities is presented. The proposed scheme has been designed to simulate the spatiotemporal transmission process. In the model, simulated agents make decisions depending on the programmed rules. Such rules correspond to spatial patterns and infection conditions under which agents interact to characterize the transmission process. The model also includes an individual profile for each agent, which defines its main social characteristics and health conditions used during its interactions. In general, this profile partially determines the behavior of the agent during its interactions with other individuals. Several hypothetical scenarios have been considered to show the performance of the proposed model. Experimental results have demonstrated that the simulations provide useful information to produce strategies for reducing the transmission risks of COVID-19 within the facilities.


Virus respiratorios: los más frecuentes, los más olvidados


title: Structure-based discovery of inhibitors of the YycG histidine kinase: New chemical leads to combat Staphylococcus epidermidis infections

text: BACKGROUND: Coagulase-negative Staphylococcus epidermidis has become a major frequent cause of infections in relation to the use of implanted medical devices. The pathogenicity of S. epidermidis has been attributed to its capacity to form biofilms on surfaces of medical devices, which greatly increases its resistance to many conventional antibiotics and often results in chronic infection. It has an urgent need to design novel antibiotics against staphylococci infections, especially those can kill cells embedded in biofilm. RESULTS: In this report, a series of novel inhibitors of the histidine kinase (HK) YycG protein of S. epidermidis were discovered first using structure-based virtual screening (SBVS) from a small molecular lead-compound library, followed by experimental validation. Of the 76 candidates derived by SBVS targeting of the homolog model of the YycG HATPase_c domain of S. epidermidis, seven compounds displayed significant activity in inhibiting S. epidermidis growth. Furthermore, five of them displayed bactericidal effects on both planktonic and biofilm cells of S. epidermidis. Except for one, the compounds were found to bind to the YycG protein and to inhibit its auto-phosphorylation in vitro, indicating that they are potential inhibitors of the YycG/YycF two-component system (TCS), which is essential in S. epidermidis. Importantly, all these compounds did not affect the stability of mammalian cells nor hemolytic activities at the concentrations used in our study. CONCLUSION: These novel inhibitors of YycG histidine kinase thus are of potential value as leads for developing new antibiotics against infecting staphylococci. The structure-based virtual screening (SBVS) technology can be widely used in screening potential inhibitors of other bacterial TCSs, since it is more rapid and efficacious than traditional screening technology.


title: The role of lipocalin-2 in age-related macular degeneration (AMD)

text: Lipocalins are a family of secreted adipokines which play important roles in various biological processes. Lipocalin-2 (LCN-2) has been shown to be involved in acute and chronic inflammation. This particular protein is critical in the pathogenesis of several diseases including cancer, diabetes, obesity, and multiple sclerosis. Herein, we discuss the general molecular basis for the involvement of LCN-2 in acute infections and chronic disease progression and also ascertain the probable role of LCN-2 in ocular diseases, particularly in age-related macular degeneration (AMD). We elaborate on the signaling cascades which trigger LCN-2 upregulation in AMD and suggest therapeutic strategies for targeting such pathways. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00018-019-03423-8) contains supplementary material, which is available to authorized users.


title: Intrinsic antibody-dependent enhancement of microbial infection in macrophages: disease regulation by immune complexes

text: A wide range of microorganisms can replicate in macrophages, and cell entry of these pathogens via non-neutralising IgG antibody complexes can result in increased intracellular infection through idiosyncratic Fcγ-receptor signalling. The activation of Fcγ receptors usually leads to phagocytosis. Paradoxically, the ligation of monocyte or macrophage Fcγ receptors by IgG immune complexes, rather than aiding host defences, can suppress innate immunity, increase production of interleukin 10, and bias T-helper-1 (Th1) responses to Th2 responses, leading to increased infectious output by infected cells. This intrinsic antibody-dependent enhancement (ADE) of infection modulates the severity of diseases as disparate as dengue haemorrhagic fever and leishmaniasis. Intrinsic ADE is distinct from extrinsic ADE, whereby complexes of infectious agents with non-neutralising antibodies lead to an increased number of infected cells. Intrinsic ADE might be involved in many protozoan, bacterial, and viral infections. We review insights into intracellular mechanisms and implications of enhanced pathogenesis after ligation of macrophage Fcγ receptors by infectious immune complexes.


Ebola: what lessons for the International Health Regulations?


title: MDCK and Vero cells for influenza virus vaccine production: a one-to-one comparison up to lab-scale bioreactor cultivation

text: Over the last decade, adherent MDCK (Madin Darby canine kidney) and Vero cells have attracted considerable attention for production of cell culture-derived influenza vaccines. While numerous publications deal with the design and the optimization of corresponding upstream processes, one-to-one comparisons of these cell lines under comparable cultivation conditions have largely been neglected. Therefore, a direct comparison of influenza virus production with adherent MDCK and Vero cells in T-flasks, roller bottles, and lab-scale bioreactors was performed in this study. First, virus seeds had to be adapted to Vero cells by multiple passages. Glycan analysis of the hemagglutinin (HA) protein showed that for influenza A/PR/8/34 H1N1, three passages were sufficient to achieve a stable new N-glycan fingerprint, higher yields, and a faster increase to maximum HA titers. Compared to MDCK cells, virus production in serum-free medium with Vero cells was highly sensitive to trypsin concentration. Virus stability at 37 °C for different virus strains showed differences depending on medium, virus strain, and cell line. After careful adjustment of corresponding parameters, comparable productivity was obtained with both host cell lines in small-scale cultivation systems. However, using these cultivation conditions in lab-scale bioreactors (stirred tank, wave bioreactor) resulted in lower productivities for Vero cells.


title: Emerging horizon for bat borne viral zoonoses

text: Bats are the only flying placental mammals that constitute the second largest order of mammals and present all around the world except in Arctic, Antarctica and a few oceanic islands. Sixty percent of emerging infectious diseases originating from animals are zoonotic and more than two-thirds of them originate in wildlife. Bats were evolved as a super-mammal for harboring many of the newly identified deadly diseases without any signs and lesions. Their unique ability to fly, particular diet, roosting behavior, long life span, ability to echolocate and critical susceptibility to pathogens make them suitable host to harbor numerous zoonotic pathogens like virus, bacteria and parasite. Many factors are responsible for the emergence of bat borne zoonoses but the most precipitating factor is human intrusions. Deforestation declined the natural habitat and forced the bats and other wild life to move out of their niche. These stressed bats, having lost foraging and behavioral pattern invade in proximity of human habitation. Either directly or indirectly they transmit the viruses to humans and animals. Development of fast detection modern techniques for viruses from the diseased and environmental samples and the lessons learned in the past helped in preventing the severity during the latest outbreaks.


title: Clinical Features of COVID-19 in a Young Man with Massive Cerebral Hemorrhage—Case Report

text: COVID-19 is currently a pandemic in the world, can invade multiple systems, and has a high morbidity and mortality. So far, no cases of acute cerebrovascular disease have been reported. This article reports the clinical features of a COVID-19 patient whose first symptom was cerebral hemorrhage. More importantly, after the craniotomy, the patient had high fever and it was difficult to retreat. After cerebrospinal fluid testing, it was determined that an intracranial infection had occurred. After anti-infection and plasma infusion of the recovered person, the patient’s symptoms gradually improved. This case suggests that COVID-19 may infringe on cerebral blood vessels and cause cerebral hemorrhage. Transfusion of plasma from rehabilitation patients is effective for critically ill patients.


title: Digital Epidemiology: Use of Digital Data Collected for Non-epidemiological Purposes in Epidemiological Studies

text: OBJECTIVES: We reviewed digital epidemiological studies to characterize how researchers are using digital data by topic domain, study purpose, data source, and analytic method. METHODS: We reviewed research articles published within the last decade that used digital data to answer epidemiological research questions. Data were abstracted from these articles using a data collection tool that we developed. Finally, we summarized the characteristics of the digital epidemiological studies. RESULTS: We identified six main topic domains: infectious diseases (58.7%), non-communicable diseases (29.4%), mental health and substance use (8.3%), general population behavior (4.6%), environmental, dietary, and lifestyle (4.6%), and vital status (0.9%). We identified four categories for the study purpose: description (22.9%), exploration (34.9%), explanation (27.5%), and prediction and control (14.7%). We identified eight categories for the data sources: web search query (52.3%), social media posts (31.2%), web portal posts (11.9%), webpage access logs (7.3%), images (7.3%), mobile phone network data (1.8%), global positioning system data (1.8%), and others (2.8%). Of these, 50.5% used correlation analyses, 41.3% regression analyses, 25.6% machine learning, and 19.3% descriptive analyses. CONCLUSIONS: Digital data collected for non-epidemiological purposes are being used to study health phenomena in a variety of topic domains. Digital epidemiology requires access to large datasets and advanced analytics. Ensuring open access is clearly at odds with the desire to have as little personal data as possible in these large datasets to protect privacy. Establishment of data cooperatives with restricted access may be a solution to this dilemma.


title: Chapter 2 Metabolism and population dynamics of the intestinal microflora in the growing pig

text: Publisher Summary This chapter discusses the available information on population dynamics of the intestinal flora in growing pigs and addresses the factors involved in changes of this flora during different stages of the animal's life and in health and disease. The intestinal flora of pigs contains several hundred microbial species, mostly strict anaerobes. A great amount of these bacteria reside in the large intestine that in adult pigs consists of mainly Gram-positive bacteria such as cocci, lactobacilli, eubacteria, and clostridia. The composition of the intestinal microflora is a result of the interaction between the microorganisms that colonize the gut and the intestinal physiology of the pigs. While a part of this microflora is constantly present in the gut (resident flora), some microorganisms have a short residence and dynamically change the composition of the microflora. The stability and diversity of this flora has a tremendous role in maintaining the health status of the pigs, especially during the suckling and post-weaning period. The digestive tract of the newborn piglet is specialized on a diet comprising milk. Therefore, a high lactase activity is present in the small intestine, at least for as long as milk comprises the dominant feed source. While several methods, including molecular-based techniques, are available to detect and identify unculturable bacterial flora of the gut, there is a need for more advanced techniques to measure the functional status of the normal flora in response to dietary feed and environmental stress.


title: Musashi1 RNA-Binding Protein Regulates Oligodendrocyte Lineage Cell Differentiation and Survival

text: Expression of Musashi1 (Msi1), an evolutionarily conserved RNA-binding protein, in neural stem cells of the subventricular zone in the postnatal and adult CNS indicates a potential role in the generation of oligodendrocytes. We now show Msi1 expression in a subset of oligodendrocyte progenitor (OP) cells in white matter areas temporally and spatially associated with oligodendrogenesis in the postnatal CNS. Msi1 function was evaluated by infection of OP cells with retroviral transduction of Msi1 or knockdown of endogenous Msi1. Retroviral expression of Msi1 significantly reduced the proportion of mature oligodendrocytes generated from OP cells in vitro and in vivo during myelination. Msi1 transduction also promoted OP survival, particularly under conditions of challenge from oxidative stress, while Msi1 siRNA knockdown resulted in dramatic OP cell death. Furthermore, in experimental demyelination Msi1 expression was increased among cells associated with lesions, including OP cells, indicating a potential role in the generation of remyelinating oligodendrocytes.


Correction: Corrigendum: A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence


COVID19: Challenging tissue viability in both patients and clinicians


title: Biologics in Rhinology – Forthcoming Personalized Concepts: the Future Starts Today

text: Sinunasale Erkrankungen zählen mit zu den häufigsten chronischen Erkrankungen und führen zu einer erheblichen Störung der Lebensqualität, ein komorbides Asthma ist häufig. Trotz leitliniengerechter Therapie ist anzunehmen, dass mind. 20% der Patienten ihre Erkrankungssymptome nicht adäquat kontrollieren können. Neben den etablierten chirurgischen und konservativen Therapieoptionen finden sich nun vielversprechende Therapieansätze, die bspw. mittels therapeutischer Antikörper mechanistisch gezielt in die Pathophysiologie der Erkrankungen eingreifen können. Die Auswahl der geeigneten Patienten durch geeignete Biomarker und die richtige Therapie zum richtigen Stadium der Erkrankung anbieten zu können, ist das Ziel stratifizierter Medizin und eine wichtige Perspektive für die HNO.Chronic diseases of the nose and the paranasal sinuses are most common, frequently associated with bronchial asthma, and result in substantial reduction of quality of life. Despite optimal treatment according to guidelines, approx. 20 % of the patients will report inadequate control of symptoms. Apart from well established surgical and conservative approaches in therapy new therapeutic antibodies are available that aim specifically pathophysiological targets. The optimal allocation of effective therapy for patients using appropriate biomarkers at the most suitable timepoint is the hallmark of stratified medicine and an important perspective in ENT.


Microbicidal Actives with Virucidal Efficacy against SARS-CoV-2


title: Macrolides in critically ill patients with Middle East Respiratory Syndrome

text: Abstract Objectives Macrolides have been reported to be associated with improved outcomes in patients with viral pneumonia related to influenza and other viruses, possibly because of their immune-modulatory effects. Macrolides have frequently been used in patients with Middle East Respiratory Syndrome (MERS). This study investigated the association of macrolides with 90-day mortality and MERS coronavirus (CoV) RNA clearance in critically ill patients with MERS. Methods This retrospective analysis of a multicenter cohort database included 14 tertiary-care hospitals in five cities in Saudi Arabia. Multivariate logistic-regression analysis was used to determine the association of macrolide therapy with 90-day mortality, and the Cox-proportional hazard model to determine the association of macrolide therapy with MERS-CoV RNA clearance. Results Of 349 critically ill MERS patients, 136 (39%) received macrolide therapy. Azithromycin was most commonly used (97/136; 71.3%). Macrolide therapy was commonly started before the patient arrived in the intensive care unit (ICU) (51/136; 37.5%), or on day1 in ICU (53/136; 39%). On admission to ICU, the baseline characteristics of patients who received and did not receive macrolides were similar, including demographic data and sequential organ failure assessment score. However, patients who received macrolides were more likely to be admitted with community-acquired MERS (P =0.02). Macrolide therapy was not independently associated with a significant difference in 90-day mortality (adjusted odds ratio [OR]: 0.84; 95% confidence interval [CI] :0.47–1.51; P =0.56) or MERS-CoV RNA clearance (adjusted HR: 0.88; 95% CI:0.47–1.64; P =0.68). Conclusions These findings indicate that macrolide therapy is not associated with a reduction in 90-day mortality or improvement in MERS-CoV RNA clearance.


title: Duration of viral shedding in asymptomatic or mild cases of novel coronavirus disease 2019 (COVID-19) from a cruise ship: A single-hospital experience in Tokyo, Japan

text: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the cause of novel coronavirus disease 2019 (COVID-19) first reported in Wuhan, China, has spread across the world, and has been characterized as a global pandemic. The propagation from asymptomatic polymerase chain reaction (PCR)-positive individuals represents a complicating factor in the efforts to control the COVID-19 pandemic. We examined the course of PCR assays and duration of viral shedding in 23 asymptomatic or mild COVID-19 patients from the cruise ship who were admitted to our hospital. Among these 23 cases, the median duration of viral shedding was 19 days (range, 6-37 days) from initial viral detection. Eight cases (35%) had another positive PCR result after testing negative once. Although the duration of viral shedding was approximately 3 weeks, the infectivity and transmissibility period from asymptomatic and mild COVID-19 cases is unclear. Further studies are needed to determine how long such asymptomatic and mild COVID-19 cases have the infectivity.


L’apnée du sommeil : une maladie ou un syndrome ?


title: A Laboratory Evaluation of Medicinal Herbs Used in China for the Treatment of Hand, Foot, and Mouth Disease

text: Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the causative agents of hand, foot, and mouth disease (HFMD). During recent epidemics of HFMD in China, medicinal herbals and preparations containing herbal extracts have demonstrated therapeutic efficacy with relative safety profiles. There have been no microbiological studies to validate their usefulness for HFMD. We selected 12 commonly used herbs for HFMD from government recommended guidelines as well as published reports and tested for their antiviral activity and anti-inflammatory activity. A water extract of Houttuynia cordata Thunb. (HCT) inhibited EV71 infection significantly and was marginally active against CVA16 infection. The IC(50) (concentration to have 50% inhibitory effect) values of HCT against a Fuyang strain and a BrCr strain of EV71 were determined at 8.9 μg/mL and 20.6 μg/mL, respectively. Mentha haplocalyx Briq. (MHB) water extract was active against CVA16, with an IC(50) value of 70.3 μg/mL. The extract did not exhibit activity against EV71 infection. Although the majority of the extracts showed no activity against viral infection, several extracts demonstrated activity in blocking proinflammatory response by viral infection. This study therefore validates the effectiveness of Chinese herbs for HFMD since some formulations containing the correct combination of the herbs can block viral replication as well as proinflammatory response of HFMD.


Asma y EPOC en pacientes hospitalizados por COVID-19


title: Expression patterns in feline blood and tissues of α(1)-acid glycoprotein (AGP) and of an AGP-related protein (AGPrP)

text: α(1)-Acid glycoprotein (AGP) is an acute-phase protein (APP) that modulates immune responses, probably – at least in humans – owing to the modification of its glycosylation pattern. On this perspective, feline AGP can be a useful comparative model, as it has different concentrations in cats susceptible or resistant to some disease. As a preliminary approach to the study of feline AGP (fAGP) we have purified this protein from feline serum by HPLC using human AGP (hAGP) as a model. Immunoblotting with a polyclonal antibody against fAGP and with a monoclonal antibody against hAGP was performed on serum from healthy cats, from cats exposed to feline coronavirus (FCoV) infection and from cats with purulent inflammations, such as feline infectious peritonitis (FIP), feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV). Immunohistochemistry on tissues from healthy cats and from cats with different diseases (FIP, FIV, FeLV, locally extensive inflammation) was also performed with the same antibodies. Both hAGP and fAGP have been purified to homogenity as determined by SDS-PAGE. fAGP did not react with the anti-hAGP antibody which, in contrast, detected in feline serum a low MW protein that we called fAGP-related protein (fAGPrP). This protein was underexpressed in cats with FeLV and FIP. Both fAGP and fAGPrP were immunohistochemically detected in plasma and hepatocytes with a stronger intensity in cats with FIP and some inflammatory conditions. Moreover, fAGPrP was detected in the cytoplasm of tissue cells, most likely identifiable with plasma cells. These cells were rarely detectable in cats with FIV and FeLV, and numerous in cats with FIP and with locally extensive inflammation. In conclusion, purified fAGP has physicochemical characteristics similar to those of hAGP, but does not cross-react with anti-hAGP antibodies. In contrast, the anti-hAGP detected an AGP-related protein whose blood concentration and tissue distribution was not related to that of fAGP. Moreover, both fAGP and fAGPrP were differently expressed in cats with pathologic conditions compared to controls. Further study of these proteins by analysing their structural characteristics is required.


title: Viral and bacterial investigations on the aetiology of recurrent pig neonatal diarrhoea cases in Spain

text: BACKGROUND: Neonatal diarrhoea represents a major disease problem in the early stages of animal production, increasing significantly pre-weaning mortality and piglets weaned below the target weight. Enteric diseases in newborn piglets are often of endemic presentation, but may also occur as outbreaks with high morbidity and mortality. The objective of this study was to assess the frequency of different pathogens involved in cases of recurrent neonatal diarrhoea in Spain. RESULTS: A total of 327 litters from 109 sow farms located in Spain with neonatal recurrent diarrhoea were sampled to establish a differential diagnosis against the main enteric pathogens in piglets. In total, 105 out of 109 (96.3%) case submissions were positive to one of the examined enteric organisms considered potentially pathogenic (Escherichia coli, Clostridium perfringens types A and C, Transmissible gastroenteritis virus [TGEV], Porcine epidemic diarrhoea virus [PEDV] or Rotavirus A [RVA]). Fifty-eight out of 109 (53.2%) submissions were positive for only one of these pathogens, 47 out of 109 (43.1%) were positive for more than one pathogen and, finally, 4 out of 109 (3.7%) were negative for all these agents. Escherichia coli strains were isolated from all submissions tested, but only 11 of them were classified into defined pathotypes. Clostridium perfringens type A was detected in 98 submissions (89.9%) and no C. perfringens type C was found. Regarding viruses, 47 (43.1%) submissions were positive for RVA, 4 (3.7%) for PEDV and none of them for TGEV. CONCLUSION: In conclusion, C. perfringens type A, E. coli and RVA were the main pathogens found in faeces of neonatal diarrheic piglets in Spain.


title: The Role of Anticoagulation in COVID-19-Induced Hypercoagulability

text: PURPOSE OF REVIEW: We aim to provide a comprehensive analysis of hypercoagulability in individuals affected by COVID-19. Our goal is to describe the hypercoagulable state related to the infection and provide guidance regarding the possible benefits of anti-coagulation with the support of evidence from current literature. RECENT FINDINGS: The incidence of thrombotic disease in individuals affected by COVID-19 is reported as high as 31%. A significant mortality benefit has been observed with the use of therapeutic anticoagulation in high-risk individuals. Literature supports the use of scoring systems, such as the sepsis-induced coagulopathy score, to risk-stratify individuals who might benefit from anticoagulation. SUMMARY: COVID-19-induced hypercoagulability has been demonstrated to play a significant role in overall COVID-19 outcomes. Current literature shows promising evidence with the use of therapeutic anticoagulation in high-risk individuals. Further studies are needed to better analyze the risks and benefits of anticoagulation in this specific patient population.


title: Lassa virus diversity and feasibility for universal prophylactic vaccine

text: Lassa virus (LASV) is a highly prevalent mammarenavirus in West Africa and is maintained in nature in a persistently infected rodent host, Mastomys natalensis, which is widely spread in sub-Saharan Africa. LASV infection of humans can cause Lassa fever (LF), a disease associated with high morbidity and significant mortality. Recent evidence indicates an LASV expansion outside its traditional endemic areas. In 2017, the World Health Organization (WHO) included LASV in top-priority pathogens and released a Target Product Profile (TPP) for vaccine development. Likewise, in 2018, the US Food and Drug Administration added LF to a priority review voucher program to encourage the development of preventive and therapeutics measures. In this article, we review recent progress in LASV vaccine research and development with a focus on the impact of LASV genetic and biological diversity on the design and development of vaccine candidates meeting the WHO’s TPP for an LASV vaccine.


title: Autopsia clínica en Síndrome Respiratorio Agudo Severo por SARS-CoV-2. Primer fallecido conocido en España

text: Resumen El nuevo coronavirus SARS-CoV-2, identificado inicialmente en China en diciembre de 2019 puede cursar con un Síndrome Respiratorio Agudo Severo (SARS) con daño alveolar masivo y fracaso respiratorio progresivo. Presentamos los hallazgos más relevantes encontrados en la autopsia clínica efectuada en nuestro hospital (Hospital Arnau de Vilanova-Lliria de Valencia) a fecha de 14 de febrero de 2020, al primer paciente fallecido conocido en España por neumonía COVID-19. A nivel pulmonar, la autopsia revela cambios típicos de daño alveolar difuso (DAD) en fase exudativa y fase proliferativa. Se observan células multinucleadas gigantes, células tipo smudge intraalveolares y trombosis vasculares. El diagnóstico microbiológico confirmativo mediante PCR se realizó 15 días después de la autopsia sobre la muestra faríngea del enfermo tomada durante su ingreso. Abstract The new coronavirus SARS-CoV-2, first identified in Wuhan, China in December, 2019, can cause Severe Acute Respiratory Syndrome (SARS) with massive alveolar damage and progressive respiratory failure. We present the relevant autopsy findings of the first patient known to have died from COVID19 pneumonia in Spain, carried out on the 14th of February, 2020, in our hospital (Hospital Arnau de Vilanova-Lliria, Valencia). Histological examination revealed changes typical of diffuse alveolar damage (DAD) in both the exudative and proliferative phase of acute lung injury. Intra-alveolar multinucleated giant cells, smudge cells and vascular thrombosis were present. The diagnosis was confirmed by reverse real-time PCR assay on a throat swab sample taken during the patient’s admission. The positive result was reported fifteen days subsequent to autopsy.


title: When being positive might be negative: An analysis of Australian and New Zealand newspaper framing of vaccination post Australia's No Jab No Pay legislation

text: Vaccination rates are an ongoing global concern. Many developing and developed countries have rates of vaccination below rates required for herd immunity, for differing reasons. One way in which to communicate information about vaccination to the wider public is via the use of the news media. Communication agenda-setting and framing theory generally hold that the news media sets the issues of importance to society and also tells us how we should think about those issues. Emphasis framing theory however, would suggest that positively-framed statements in the media may actually be viewed as persuasive in a coercing way, leading to resistance to the messages. Further, this theory claims that negative news media is viewed as more credible and therefore, more easily accepted. We were interested to explore the framing of news reports about vaccination and the potential effects this framing may have had on the wider public over the years 2016–2017 in both Australia and New Zealand (when changes in vaccination policy and publicity respectively were on the agenda). We undertook a content analysis of 197 articles and emphasis frame, type of message, and other variables recorded. In both Australia and New Zealand, the news media messages were predominately positively framed and yet the vaccination rates of New Zealand particularly (where no policy changes mandating vaccination took place) have been decreasing. We suggest the media emphasis on positive vaccination reporting may be having the opposite effect of engendering resistance to vaccination within those who are vaccine-hesitant.


title: COVID-19-Related Information Sources and the Relationship With Confidence in People Coping with COVID-19: Facebook Survey Study in Taiwan

text: BACKGROUND: People obtain information on the coronavirus disease (COVID-19) from the internet and other sources. Understanding the factors related to such information sources aids health professionals in educating individuals. OBJECTIVE: This study used data collected from the online survey study on COVID-19 in Taiwan to examine what major COVID-19 information sources are available and which sources are significantly related to the self-confidence of people in coping with COVID-19 in Taiwan. METHODS: A total of 1904 participants (1270 non–health-care workers and 634 health care workers) were recruited from the Facebook advertisement. Their major sources of information about COVID-19, the relationships between the sources and demographic factors, and the relationships between the sources and the self-confidence in coping with COVID-19 were surveyed. RESULTS: Most Taiwanese people relied on the internet for COVID-19 information. Many respondents also used a variety of sources of information on COVID-19; such variety was associated with sex, age, and the level of worry toward COVID-19, as well as if one was a health care worker. For health care workers, the use of formal lessons as an information source was significantly associated with better self-confidence in coping with COVID-19. The significant association between receiving information from more sources and greater self-confidence was found only in health care workers but not in non–health-care workers. CONCLUSIONS: Medical professionals should consider subgroups of the population when establishing various means to deliver information on COVID-19.


title: Manifestations cutanées des maladies internes du chien

text: Résumé Les manifestations cutanées des maladies internes commencent à être bien connues chez le chien, même si leur étiologie et leur pathogénie ne sont pas toujours élucidées. Elles sont d'une très grande diversité clinique et en relation avec des maladies internes variées. Leur connaissance est importante car ces lésions cutanées entrent dans de nombreux diagnostics différentiels et apparaissent, pour certaines, précocement avant les symptômes de la maladie interne sous-jacente. Enfin, certaines de ces manifestations cutanées constituent des syndromes paranéoplasiques cutanés. Sont envisagées la dermatofibrose nodulaire, l'érythème nécrolytique migrant, la dermatomyosite, les calcinoses, les amyloses, les xanthomes cutanés, le syndrome d'automutilation podale et le syndrome syringomyélie. Summary Cutaneous lesions associated with internal diseases have become well-known in dogs, even if the circumstances in which they appear are not always known. They have a various clinic diversity which is related to the numerous internal diseases. Their knowledge is important since these cutaneous lesions appear in numerous differential diagnoses; some of them occur before the symptoms of the underlying disease. Finally, some constitute cutaneous paraneoplastic syndromes. The following diseases are considered: nodular dermatofibrosis, migratory necrolytic erythema, dermatomyositis, calcinosis cutis, cutaneous amyloidosis, cutaneous xanthomas, self-mutilation foot syndrome and syringohydromyelia syndrome.


title: X-ray Structure and Enzymatic Activity Profile of a Core Papain-like Protease of MERS Coronavirus with utility for structure-based drug design

text: Ubiquitin-like domain 2 (Ubl2) is immediately adjacent to the N-terminus of the papain-like protease (PLpro) domain in coronavirus polyproteins, and it may play a critical role in protease regulation and stability as well as in viral infection. However, our recent cellular studies reveal that removing the Ubl2 domain from MERS PLpro has no effect on its ability to process the viral polyprotein or act as an interferon antagonist, which involves deubiquitinating and deISGylating cellular proteins. Here, we test the hypothesis that the Ubl2 domain is not required for the catalytic function of MERS PLpro in vitro. The X-ray structure of MERS PLpro-∆Ubl2 was determined to 1.9 Å and compared to PLpro containing the N-terminal Ubl2 domain. While the structures were nearly identical, the PLpro-∆Ubl2 enzyme revealed the intact structure of the substrate-binding loop. Moreover, PLpro-∆Ubl2 catalysis against different substrates and a purported inhibitor revealed no differences in catalytic efficiency, substrate specificity, and inhibition. Further, no changes in thermal stability were observed between enzymes. We conclude that the catalytic core of MERS PLpro, i.e. without the Ubl2 domain, is sufficient for catalysis and stability in vitro with utility to evaluate potential inhibitors as a platform for structure-based drug design.


title: Permission to hustle: Igniting entrepreneurship in an organization

text: Abstract Perceived institutional barriers, especially in existing organizations, often impede entrepreneurial action in the face of crisis and uncertainty. Understanding how collective entrepreneurial action occurs despite deeply institutionalized mindsets is important to advance entrepreneurship theory. We report on an autoethnographic account of an entrepreneurship professor and several colleagues who gave themselves permission to hustle to overcome perceived institutional barriers to entrepreneurial action. As the findings reveal, a permission to hustle mindset provided a platform for the group of professors to act entrepreneurially in response to the COVID-19 pandemic. In a matter of several days, the group acted under uncertainty to create a new “idea blitz” program which attracted over 150 participants from around the world. We argue that permission to hustle is an important sense-breaking device that ignites and sustains entrepreneurial action by breaking taken-for-granted assumptions about institutionalized practices and redirecting attention toward urgent and creative action, especially in existing organizations where institutional barriers are perceived to impede such action.


title: Calming Cytokine Storm in Pneumonia by Targeted Delivery of TPCA-1 Using Platelet-derived Extracellular Vesicles

text: Summary Pneumonia can cause high morbidity and mortality due to the uncontrolled inflammation in the lung tissue. Calming the cytokine storm may be one key to save the life of patients with severe pneumonia. Here, inspired by the intrinsic affinity of platelets to the site of inflammation, we have engineered platelet-derived extracellular vesicles (PEVs) for pneumonia-targeted drug delivery. It is demonstrated that PEVs that are easily generated from the activated platelets can selectively target pneumonia in the mice model with acute lung injury (ALI). By loading with [5-(p-Fluorophenyl)-2-ureido] thiophene-3-carboxamide (TPCA-1) that can inhibit the production of inflammatory factors, the PEVs significantly improve therapeutic benefits by inhibiting the pulmonary inflammatory cells infiltration, and calming local cytokine storm compared with the free drug-treated group. Furthermore, we find that PEVs could serve as a broad platform that can selectively target various inflammatory sites, including chronic atherosclerotic plaque, rheumatoid arthritis and wound associated with skin.


title: Efficacy of cineole in patients suffering from acute bronchitis: a placebo-controlled double-blind trial

text: OBJECTIVE: Cineole has mucolytic, bronchodilating and anti-inflammatory properties and reduces the exacerbation rate in patients suffering from COPD, as well as ameliorates symptoms in patients suffering from asthma and rhinosinusitis. Based on these effects, we therefore postulated the hypothesis that patients with acute bronchitis would also benefit from therapy with Cineole. METHODS: As part of a double-blind, placebo-controlled, multi-center-study, a total of 242 patients with confirmed acute bronchitis was randomly selected to participate. Over a period of 10 days, all patients were administered 3 x 200 mg of Cineole, or a respective placebo, per day. The primary outcome measure was a Bronchitis Sum Score, which summarises the relevant symptoms of acute bronchitis. RESULTS: After 4 days of treatment it was notable, that the patient group treated with Cineole, showed significantly more improvements of the bronchitis-sum-score than those of the placebo group (p = 0.0383). The statistical significant difference of the individual outcome measures was especially underlined by the frequency of cough fits by p = 0.0001 after 4 days. CONCLUSIONS: The effects of Cineole in the treatment of acute bronchitis were clearly measurable and could be proven after a treatment period of merely 4 days. This study corroborates the fact that Cineole actively and significantly reduces cough frequency after four days. Therefore it has been shown to have a great socioeconomic impact. TRIAL REGISTRATION: ISRCTN: ISRCTN37784439


docid: efxjxtgu

title: Urban Health: An Overview

text: For the first time in history, over half the world's population resides in urban areas. The challenge of urban health is already central to the social development of cities and this challenge will continue to grow as the urbanization trend continues. Urban health, particularly in the world's most rapidly urbanizing regions – the low- and middle-income countries referred to as the Global South – is largely determined by social and environmental factors, which are strongly interrelated. These include but are not limited to access to basic services and amenities associated with urban living, such as health care, transport, clean water, sanitation, education, and safe places to live and work. Climate change-related events, such as severe storms and floods, are interacting with and compounding existing urban health risks. Transport-related injuries and deaths are expected to increase as more vehicles are added to the already-chaotic fray of urban traffic. Addressing the urban health challenge will require an approach that focuses on the social and environmental determinants that drive health outcomes and understanding the complex interactions among them in the urban context.


title: Risk of Maternal Feacal Contamination and How to Reduce the Potential Risk of Vertical Transmission of SARS-Cov-2 during Vaginal Delivery?>

text: The risk of vertical transmission during vaginal delivery in COVID-19 pregnant patients is currently a topic of debate. Obstetric norms on vaginal birth assistance to reduce the potential risk of perinatal infection should be promoted by ensuring that the risk of contamination from maternal faecal material is reduced during vaginal delivery.


title: BRACHYTHERAPY ISSUES AND PRIORITIES IN THE CONTEXT OF COVID-19 OUTBREAK

text: Brachytherapy has a major role in patient’s cure and cannot be substituted or excessively delayed in rapidly growing tumors (e.g.; cervical cancer). However, COVID-19 pandemic infection requires workflow adaptation in order to ensure treatment continuity for patients while ensuring safety of health care professionals. Because of a drastic reduction of all operating room capacity with exception of critical emergencies, it is mandatory to have COVID-19 recommendations applicable to the field of brachytherapy, taking into account specific constraints. Strategies for infection prevention and rationalization of health care resources are discussed. Herein we place brachytherapy in the context of reduced access to radiotherapy facilities and underscore strategies to be implemented in order to protect patients and health workers while ensuring that patients will still receive the most appropriate curative treatment.


title: Just remember this: Lexicogrammatical relevance markers in lectures

text: Abstract This paper presents a comprehensive overview of lexicogrammatical devices which highlight important or relevant points in lectures. Despite the established usefulness of discourse organizational cues for lecture comprehension and note-taking, very little is known about the marking of relevance in this genre. The current overview of lexicogrammatical relevance markers combines a qualitative and quantitative investigation of 160 lectures from the British Academic Spoken English (BASE) corpus. These markers could mostly be classified according to their main element into adjective, noun, verb and adverb patterns. Verb patterns were the most common, followed by noun patterns. The verb pattern V clause (e.g., remember slavery had already been legally abolished) and the noun pattern MN v-link (e.g., the point is) are the predominant types of relevance markers. The discrepancy between the prevalent markers and what may be thought of as prototypical or included in EAP textbooks as relevance markers also demonstrates the need for corpus linguistic research. Implications for EAP course design, teaching English for lecturing purposes, and educational research are discussed.


title: Recent Advances in Nanoparticle Concentration and Their Application in Viral Detection Using Integrated Sensors

text: Early disease diagnostics require rapid, sensitive, and selective detection methods for target analytes. Specifically, early viral detection in a point-of-care setting is critical in preventing epidemics and the spread of disease. However, conventional methods such as enzyme-linked immunosorbent assays or cell cultures are cumbersome and difficult for field use due to the requirements of extensive lab equipment and highly trained personnel, as well as limited sensitivity. Recent advances in nanoparticle concentration have given rise to many novel detection methodologies, which address the shortcomings in modern clinical assays. Here, we review the primary, well-characterized methods for nanoparticle concentration in the context of viral detection via diffusion, centrifugation and microfiltration, electric and magnetic fields, and nano-microfluidics. Details of the concentration mechanisms and examples of related applications provide valuable information to design portable, integrated sensors. This study reviews a wide range of concentration techniques and compares their advantages and disadvantages with respect to viral particle detection. We conclude by highlighting selected concentration methods and devices for next-generation biosensing systems.


title: Porcine β-defensin 2 inhibits proliferation of pseudorabies virus in vitro and in transgenic mice

text: BACKGROUND: Porcine β-defensin 2 (PBD-2), produced by host cells, is an antimicrobial cysteine-rich cationic peptide with multi-functions. Previous studies have demonstrated that PBD-2 can kill various bacteria, regulate host immune responses and promote growth of piglets. However, the antiviral role of PBD-2 is rarely investigated. This study aimed to reveal the antiviral ability of PBD-2 against pseudorabies virus (PRV), the causative pathogen of Aujeszky’s disease, in PK-15 cells and in a PBD-2 expressing transgenic (TG) mouse model. METHODS: In this study, the cytotoxicity of PBD-2 on PK-15 cells was measured by CCK-8 assay. PK-15 cells were incubated with PRV pre-treated with different concentrations of PBD-2 and PRV titers in cell culture supernatants were determined by real-time quantitative PCR (RT-qPCR). TG mice and wild-type (WT) mice were intraperitoneally injected with PRV and the survival rate was recorded for 10 days. Meanwhile, tissue lesions in brain, spleen and liver of infected mice were observed and the viral loads of PRV in brain, liver and lung were analyzed by RT-qPCR. RESULTS: PBD-2 at a maximum concentration of 80 μg/mL displayed no significant cytotoxicity on PK-15 cells. A threshold concentration of PBD-2 at 40 μg/mL was required to inhibit PRV proliferation in PK-15 cells. The survival rate in PBD-2 TG mice was 50% higher than that of WT mice. In addition, TG mice showed alleviated tissue lesions in brain, spleen and liver compared with their WT littermates after PRV challenge, while viral loads of PRV in brain, liver and lung of TG mice were significantly lower than that of WT mice. CONCLUSIONS: PBD-2 could inhibit PRV proliferation in PK-15 cells and protect mice from PRV infection, which confirmed the antiviral ability of PBD-2 both in vitro and in vivo. The application of PBD-2 in developing anti-viral drugs or disease-resistant animals can be further investigated.


title: The role of asymptomatic screening in the detection of recurrent ovarian cancer

text: OBJECTIVE: To investigate the utility of asymptomatic screening, including CA-125, imaging, and pelvic exam, in the diagnosis and management of recurrent ovarian cancer. METHODS: Women with ovarian cancer whose cancer recurred after remission were categorized by first method that their provider suspected disease recurrence: CA-125, imaging, symptoms, or physical exam. Differences in clinicopathologic, primary treatment characteristics, and outcomes data including secondary cytoreductive surgery (SCS) outcome and overall survival (OS) were collected. RESULTS: 102 patients were identified at our institution from 2003 to 2015. 20 recurrences were detected by symptoms, while 62 recurrences were diagnosed first by asymptomatic rise in CA-125, 5 by pelvic exam, and 15 by imaging in the absence of known exam abnormality or rise in CA-125. Mean time to recurrence was 18.9 months, and median survival was 45.8 months. These did not vary by recurrence detection method (all p > 0.4). Patients whose disease was detected by CA-125 were less likely to undergo SCS than those detected by other means (21.7% vs. 35.0%, p = 0.007). In addition to the 5 patients whose recurrence was detected primarily by pelvic exam, an additional 10 (total n = 15) patients had an abnormal pelvic exam at time of diagnosis of recurrence. DISCUSSION: Recurrence detection method was not associated with differing rates of survival or optimal SCS, however those patients detected by CA-125 were less likely to undergo SCS. The pelvic exam was a useful tool for detecting a significant proportion of recurrences.


Characteristics and outcomes of Behçet’s syndrome patients with Coronavirus Disease 2019: a case series of 10 patients


title: Off‐label use of midazolam in older inpatients: analysis of prescribing practices in a French hospital (MIDnight study)

text: The MIDnight study carried out in a geriatric hospital confirms the hypothesis of gaps between recommendations and off‐label use of drugs, like midazolam. Such gaps expose patients to risks and prescribers to legal issues. However, withdrawing midazolam would be an additional risk since it would deprive patients of an unequalled drug. The authors of the article [1] chose to deal with this dilemma in a multi‐phase evaluation program aimed at analyzing practices, understanding use factors, and producing recommendations to make prescriptions and their use in the elderly safer.


463. Coronaviruses Are Able to Efficiently Eradicate Human Tumor Cells if Provided with the Appropriate Virus Receptor


Estimando el número de casos de COVID-19 a tiempo real utilizando un formulario web a través de las redes sociales: Proyecto COVID19-TRENDS


docid: hnbgaxft

title: Chapter 17 Current therapeutics and prophylactic approaches to treat pneumonia

text: Abstract Bacterial pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Mycoplasma pneumoniae, and Klebsiella pneumoniae represents a frequent cause of mortality worldwide. The increased incidence of pneumococcal diseases in both developed and developing countries is alarmingly high, affecting infants and aged adult populations. The growing rate of antibiotic resistance and biofilm formation on medical device surfaces poses a greater challenge for treating respiratory infections. Over recent years, a better understanding of bacterial growth, metabolism, and virulence has offered several potential targets for developing therapeutics against bacterial pneumonia. This chapter will discuss the current and developing trends in treating bacterial pneumonia.


title: Highly sensitive fluorogenic sensing of L-Cysteine in live cells using gelatin-stabilized gold nanoparticles decorated graphene nanosheets

text: A highly sensitive and selective fluorogenic sensing of L-Cysteine (L-Cys) was implemented based on gelatin stabilized gold nanoparticles decorated reduced graphene oxide (rGO/Au) nanohybrid. The rGO/Au nanohybrid was prepared by the one-pot hydrothermal method and well characterized by different physiochemical techniques. The nanohybrid exhibits a weak fluorescence of rGO due to the energy transfer from the rGO to Au NPs. The rGO/Au nanohybrid shows enhanced fluorescence activity due to the restoration of quenched fluorescence of rGO/Au nanohybrid in presence of L-Cys. The rGO/Au nanohybrid exhibits much lower detection limit of 0.51 nM for L-Cys with higher selectivity. The fluorescence sensing mechanism arose from the fluorescence recovery due to the stronger interaction between Au NPs and L-Cys, and consequently, the energy transfer was prevented between rGO and Au NPs. The practicability of rGO/Au sensor was implemented by invitro bioimaging measurements in Colo-205 (colorectal adenocarcinoma) and MKN-45 (gastric carcinoma) cancer live cells with excellent biocompatibility.


title: Early trends for SARS‐CoV‐2 infection in central and north Texas and impact on other circulating respiratory viruses

text: Rapid diagnosis and isolation are key to containing the quick spread of a pandemic agent like severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2), which has spread globally since its initial outbreak in Wuhan province in China. SARS‐CoV‐2 is novel and the effect on typically prevalent seasonal viruses is just becoming apparent. We present our initial data on the prevalence of respiratory viruses in the month of March 2020. This is a retrospective cohort study post launching of SARS‐CoV‐2 testing at Baylor Scott and White Hospital (BSWH), Temple, Texas. Testing for SARS‐CoV‐2 was performed by real‐time reverse transcription polymerase chain reaction assay and results were shared with State public health officials for immediate interventions. More than 3500 tests were performed during the first 2 weeks of testing for SARS‐CoV‐2 and identified 168 (4.7%) positive patients. Sixty‐two (3.2%) of the 1912 ambulatory patients and 106 (6.3%) of the 1659 emergency department/inpatients tested were positive. The highest rate of infection (6.9%) was seen in patients aged 25 to 34 years, while the lowest rate of infection was seen among patients aged <25 years old (2%). County‐specific patient demographic information was shared with respective public health departments for epidemiological interventions. Incidentally, this study showed that there was a significant decrease in the occurrence of seasonal respiratory virus infections, perhaps due to increased epidemiological awareness about SARS‐CoV‐2 among the general public, as well as the social distancing measures implemented in response to SARS‐CoV‐2. Data extracted for BSWH from the Centers for Disease Control and Prevention's National Respiratory and Enteric Virus Surveillance System site revealed that Influenza incidence was 8.7% in March 2020, compared with 25% in March 2019. This study was intended to provide an initial experience of dealing with a pandemic and the role of laboratories in crisis management. This study provided SARS‐CoV‐2 testing data from ambulatory and inpatient population. Epidemiological interventions depend on timely availability of accurate diagnostic tests and throughput capacity of such systems during large outbreaks like SARS‐CoV‐2.


title: Pediatrician, watch out for corona-phobia

text: The current outbreak of COVID-19 raging globally is taking a heavy toll on the adult population, with a rapidly growing number of newly infected and critically ill patients. However, to date, mortality rate among children is low as they mostly suffer from a mild disease. Yet, other more routinely encountered childhood diseases do not stand still and continue to be the main share of pediatricians’ everyday challenges. Here we describe a case series of routinely seen pediatric diseases with delayed diagnosis due to different aspects of what we call “Corona-phobia”. These cases were easily collected within a 1-week period which implies that this is a more widespread phenomenon. In conclusion, this raises the possibility that measures taken to mitigate this pandemic may be more damaging to children overall than the virus itself. We believe that pediatricians as well as policy makers should take this important aspect into consideration.


title: Chapter 11 Natural Vaccine Adjuvants and Immunopotentiators Derived From Plants, Fungi, Marine Organisms, and Insects

text: Abstract Immunopotentiators derived from different natural sources are under investigation with varying success. This chapter gives an overview of developments from plants, fungi, marine organisms, and insects. Plant-derived immune stimulators consist of a diverse range of small molecules or large polysaccharides. Notable examples that have been assessed in both preclinical and clinical trials include saponins, tomatine, and inulin. Similarly, fungi produce a range of potential candidate molecules, with β-glucans showing the most promise. Other complex molecules that have established adjuvant activity include α-galactosylceramide (originally obtained from a marine sponge), chitosan (commonly produced from chitin from shrimps), and peptides (found in bee venom). Some organisms, for example, endophytic fungi and bees, produce immunostimulants using compounds obtained from plants. The main challenges facing this type of research and tools being developed to overcome them are examined.


title: Microbial and histopathologic considerations in the use of mouse models of inflammatory bowel diseases

text: Abstract: Mouse models provide powerful tools to investigate disease mechanisms and are widely used in inflammatory bowel disease research. However, it is common for reports of mouse model studies to lack potentially important information about the microbial status of the mice and the method used to evaluate disease expression for statistical analysis. For example, it is common practice to state that the mice were housed under specific pathogen‐free conditions but provide no further information regarding the presence or absence of organisms such as Helicobacter spp. that are known or likely to affect disease expression, thus omitting information potentially important to the expected phenotype of the mice and their responses to experimental manipulation. We therefore encourage authors to use such terms as “conventional” and “specific pathogen‐free” precisely, to state the agents from which the mice are represented to be free, and to provide a brief description of the health monitoring protocol. Descriptions of histopathologic methods used to evaluate colitis in mouse models also often do not include sufficient detail to allow readers to understand and evaluate the methods; in addition, the lesions commonly are shown in photomicrographs that are too small and of too low resolution to be interpreted. Inasmuch as such methods are often the major or only source of data upon which conclusions regarding genotype or experimental treatment effects are based, the method employed should be fully described, and photomicrographs should be of adequate size and resolution to allow independent assessment. (Inflamm Bowel Dis 2012)