The innate immune system is paramount in the response to and clearance of influenza A virus (IAV) infection in non-immune individuals. Known factors include type I and III interferons and antiviral ...pathogen recognition receptors, and the cascades of antiviral and pro- and anti-inflammatory gene expression they induce. MicroRNAs (miRNAs) are increasingly recognized to participate in post-transcriptional modulation of these responses, but the temporal dynamics of how these players of the antiviral innate immune response collaborate to combat infection remain poorly characterized. We quantified the expression of miRNAs and protein coding genes in the lungs of pigs 1, 3, and 14 days after challenge with swine IAV (H1N2). Through RT-qPCR we observed a 400-fold relative increase in IFN-lambda3 gene expression on day 1 after challenge, and a strong interferon-mediated antiviral response was observed on days 1 and 3 accompanied by up-regulation of genes related to the pro-inflammatory response and apoptosis. Using small RNA sequencing and qPCR validation we found 27 miRNAs that were differentially expressed after challenge, with the highest number of regulated miRNAs observed on day 3. In contrast, the number of protein coding genes found to be regulated due to IAV infection peaked on day 1. Pulmonary miRNAs may thus be aimed at fine-tuning the initial rapid inflammatory response after IAV infection. Specifically, we found five miRNAs (ssc-miR-15a, ssc-miR-18a, ssc-miR-21, ssc-miR-29b, and hsa-miR-590-3p)-four known porcine miRNAs and one novel porcine miRNA candidate-to be potential modulators of viral pathogen recognition and apoptosis. A total of 11 miRNAs remained differentially expressed 14 days after challenge, at which point the infection had cleared. In conclusion, the results suggested a role for miRNAs both during acute infection as well as later, with the potential to influence lung homeostasis and susceptibility to secondary infections in the lungs of pigs after IAV infection.
Actinobacillus pleuropneumoniae causes pleuropneumonia in pigs, a disease which is associated with high morbidity and mortality, as well as impaired animal welfare. To obtain in-depth understanding ...of this infection, the interplay between virulence factors of the pathogen and defense mechanisms of the porcine host needs to be elucidated. However, research has traditionally focused on either bacteriology or immunology; an unbiased picture of the transcriptional responses can be obtained by investigating both organisms in the same biological sample.
Host and pathogen responses in pigs experimentally infected with A. pleuropneumoniae were analyzed by high-throughput RT-qPCR. This approach allowed concurrent analysis of selected genes encoding proteins known or hypothesized to be important in the acute phase of this infection. The expression of 17 bacterial and 31 porcine genes was quantified in lung samples obtained within the first 48 hours of infection. This provided novel insight into the early time course of bacterial genes involved in synthesis of pathogen-associated molecular patterns (lipopolysaccharide, peptidoglycan, lipoprotein) and genes involved in pattern recognition (TLR4, CD14, MD2, LBP, MYD88) in response to A. pleuropneumoniae. Significant up-regulation of proinflammatory cytokines such as IL1B, IL6, and IL8 was observed, correlating with protein levels, infection status and histopathological findings. Host genes encoding proteins involved in iron metabolism, as well as bacterial genes encoding exotoxins, proteins involved in adhesion, and iron acquisition were found to be differentially expressed according to disease progression. By applying laser capture microdissection, porcine expression of selected genes could be confirmed in the immediate surroundings of the invading pathogen.
Microbial pathogenesis is the product of interactions between host and pathogen. Our results demonstrate the applicability of high-throughput RT-qPCR for the elucidation of dual-organism gene expression analysis during infection. We showed differential expression of 12 bacterial and 24 porcine genes during infection and significant correlation of porcine and bacterial gene expression. This is the first study investigating the concurrent transcriptional response of both bacteria and host at the site of infection during porcine respiratory infection.
MicroRNAs (miRNAs) are a class of short regulatory RNA molecules which are implicated in modulating gene expression. Levels of circulating, cell-associated miRNAs in response to influenza A virus ...(IAV) infection has received limited attention so far. To further understand the temporal dynamics and biological implications of miRNA regulation in circulating leukocytes, we collected blood samples before and after (1, 3, and 14 days) IAV challenge of pigs. Differential expression of miRNAs and innate immune factor mRNA transcripts was analysed using RT-qPCR. A total of 20 miRNAs were regulated after IAV challenge, with the highest number of regulated miRNAs seen on day 14 after infection at which time the infection was cleared. Targets of the regulated miRNAs included genes involved in apoptosis and cell cycle regulation. Significant regulation of both miRNAs and mRNA transcripts at 14 days after challenge points to a protracted effect of IAV infection, potentially affecting the host's ability to respond to secondary infections. In conclusion, experimental IAV infection of pigs demonstrated the dynamic nature of miRNA and mRNA regulation in circulating leukocytes during and after infection, and revealed the need for further investigation of the potential immunosuppressing effect of miRNA and innate immune signaling after IAV infection.
Influenza is a viral respiratory disease having a major impact on public health. Influenza A virus (IAV) usually causes mild transitory disease in humans. However, in specific groups of individuals ...such as severely obese, the elderly, and individuals with underlying inflammatory conditions, IAV can cause severe illness or death. In this review, relevant small and large animal models for human IAV infection, including the pig, ferret, and mouse, are discussed. The focus is on the pig as a large animal model for human IAV infection as well as on the associated innate immune response. Pigs are natural hosts for the same IAV subtypes as humans, they develop clinical disease mirroring human symptoms, they have similar lung anatomy, and their respiratory physiology and immune responses to IAV infection are remarkably similar to what is observed in humans. The pig model shows high face and target validity for human IAV infection, making it suitable for modeling many aspects of influenza, including increased risk of severe disease and impaired vaccine response due to underlying pathologies such as low-grade inflammation. Comparative analysis of proteins involved in viral pattern recognition, interferon responses, and regulation of interferon-stimulated genes reveals a significantly higher degree of similarity between pig, ferret, and human compared with mice. It is concluded that the pig is a promising animal model displaying substantial human translational value with the ability to provide essential insights into IAV infection, pathogenesis, and immunity.
Background
Medication-overuse headache is prevalent, but in principle preventable.
Objective
To describe the Danish national awareness campaign for medication-overuse headache.
Methods
The Danish ...Headache Center, the Association of Danish Pharmacies, and headache patient organizations implemented a four-month medication-overuse headache awareness campaign in 2016. Target groups were the general public, general practitioners, and pharmacists. Key messages were: Overuse of pain-medication can worsen headaches; pain-medication should be used rationally; and medication-overuse headache is treatable. A range of communication technologies was used. A survey on the public’s awareness of medication-overuse headache was conducted.
Results
The Danish adult population is 4.2 million. Online videos were viewed 297,000 times in three weeks. All 400 pharmacies received campaign materials. Over 28,000 leaflets were distributed. Two radio interviews were conducted. A television broadcast about headache reached an audience of 520,000. Forty articles were published in print media. Information was accessible at 32 reputable websites and five online news agencies. Three scientific papers were published. Information was available at an annual conference of general practitioners, including a headache lecture. The survey showed an increase in percentage of the public who knew about medication-overuse headache (from 31% to 38%).
Conclusion
A concerted campaign to prevent medication-overuse headache can be implemented through involvement of key stakeholders.
Background
Patients with pre‐existing severe mental disorders are significantly less likely to receive guideline‐recommended cancer treatment and seems to have a significantly lower rate of cancer ...survival compared to patients with cancer without mental disorders.
Aim
To perform a systematic review on barriers at patient‐, provider‐ and system‐levels in cancer trajectories of patients with pre‐existing severe mental disorders.
Method
A systematic review was performed following the PRISMA guidelines (PROSPERO ID: CRD42022316020).
Results
Nine eligible studies were identified. Barriers at patient‐level included lack of self‐care and ability to recognize physical symptoms and signs. Provider‐level barriers included stigma from health care professionals on mental disorders, whereas system‐level barriers included fragmented health care and consequences of this.
Conclusion
This systematic review found that barriers at patient‐, provider‐ and system‐levels exist in cancer trajectories for patients with severe mental disorders, causing disparities in cancer care. Further research is needed to improve cancer trajectories for patients with severe mental disorder.
![IFN-[lambda] and microRNAs ...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1932-6203/small "IFN-[lambda] and microRNAs are important modulators of the pulmonary innate immune response against influenza A (H1N2) infection in pigs")
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