Btk Regulated Macrophage Polarization in Response to Lipopolysaccharide

Bacterial Lipopolysaccharide (LPS) is a strong inducer of inflammation and does so by inducing polarization of macrophages to the classic inflammatory M1 population. Given the role of Btk as a critical signal transducer downstream of TLR4, we investigated its role in M1/M2 induction. In Btk deficient (Btk−\−) mice we observed markedly reduced recruitment of M1 macrophages following intraperitoneal administration of LPS. Ex vivo analysis demonstrated an impaired ability of Btk−/− macrophages to polarize into M1 macrophages, instead showing enhanced induction of immunosuppressive M2-associated markers in response to M1 polarizing stimuli, a finding accompanied by reduced phosphorylation of STAT1 and enhanced STAT6 phosphorylation. In addition to STAT activation, M1 and M2 polarizing signals modulate the expression of inflammatory genes via differential activation of transcription factors and regulatory proteins, including NF-κB and SHIP1. In keeping with a critical role for Btk in macrophage polarization, we observed reduced levels of NF-κB p65 and Akt phosphorylation, as well as reduced induction of the M1 associated marker iNOS in Btk−/− macrophages in response to M1 polarizing stimuli. Additionally enhanced expression of SHIP1, a key negative regulator of macrophage polarisation, was observed in Btk−/− macrophages in response to M2 polarizing stimuli. Employing classic models of allergic M2 inflammation, treatment of Btk−/− mice with either Schistosoma mansoni eggs or chitin resulted in increased recruitment of M2 macrophages and induction of M2-associated genes. This demonstrates an enhanced M2 skew in the absence of Btk, thus promoting the development of allergic inflammation

Alterations and Preservations: Practices and Perspectives of Speech-Language Pathologists Regarding the Intervention of Thickened Liquids for Swallowing Problems

PURPOSE:The intervention of thickened liquids (TL) is commonly used to reduce aspiration in people with dysphagia. Speech-language pathologists (SLPs) have traditionally believed it is an effective intervention. Recent articles highlight limited evidence, poor acceptance, and a variety of unintended consequences. This study explores if current debates have been reflected in SLP practices and perspectives. METHOD: The intervention of thickened liquids (TL) is commonly used to reduce aspiration in people with dysphagia. Speech-language pathologists (SLPs) have traditionally believed it is an effective intervention. Recent articles highlight limited evidence, poor acceptance, and a variety of unintended consequences. This study explores if current debates have been reflected in SLP practices and perspectives. RESULTS: The 370 respondents represented mainly experienced, confident, hospital-based clinicians. While 20% of respondents frequently recommend TL, 61% believe it to be a burdensome treatment. “Best treatment” and “It works” beliefs continue to underpin decision making. Those who recommend TL most often are most influenced by penetration, coughing, and their own clinical experience. They are more likely to believe TL is evidence based and effective, reduces aspiration, and improves hydration. Person-centeredness is important among all respondents, although significant numbers would implement TL against patient wishes. Improvements in aspiration status and quality of life rank highly as reasons to discontinue TL. CONCLUSIONS: The results of this study suggest that fewer respondents are regularly using TL. Divergent groups are evident with those frequently employing and believing in the efficacy of TL and those who do not. While current debates are influencing practice, there clearly remains a significant number of SLPs continuing to recommend TL. This study's findings highlight both alterations and preservations in the discipline's approach to TL and calls for SLPs to reframe our thinking regarding this intervention as well as consider alternative options in this treatment space

Social work students on the island of Ireland: a cross-sectional survey

Understanding the characteristics, motivations, and experiences of student social workers is important to inform their professional education and support needs. To date, there has been relatively little research about social work students in Ireland, both North and South. This study reports on an all-Ireland survey of students beginning their social work course in Autumn 2018 in the six Universities delivering social work education. It describes the characteristics of the student cohort, examines the motivations behind choosing this career, and highlights some of the potentially relevant life experiences and beliefs which may have contributed to their ambition to join the social work profession. Implications for social work education, recommendations for curriculum development, workforce planning, and the provision of appropriate support for students are discussed

Novel Avian Influenza H7N3 Strain Outbreak, British Columbia

Genome sequences of chicken (low pathogenic avian influenza [LPAI] and highly pathogenic avian influenza [HPAI]) and human isolates from a 2004 outbreak of H7N3 avian influenza in Canada showed a novel insertion in the HA0 cleavage site of the human and HPAI isolate. This insertion likely occurred by recombination between the hemagglutination and matrix genes in the LPAI virus

Btk regulates macrophage polarization in response to lipopolysaccharide

Bacterial Lipopolysaccharide (LPS) is a strong inducer of inflammation and does so by inducing polarization of macrophages to the classic inflammatory M1 population. Given the role of Btk as a critical signal transducer downstream of TLR4, we investigated its role in M1/M2 induction. In Btk deficient (Btk (−\−)) mice we observed markedly reduced recruitment of M1 macrophages following intraperitoneal administration of LPS. Ex vivo analysis demonstrated an impaired ability of Btk(−/−) macrophages to polarize into M1 macrophages, instead showing enhanced induction of immunosuppressive M2-associated markers in response to M1 polarizing stimuli, a finding accompanied by reduced phosphorylation of STAT1 and enhanced STAT6 phosphorylation. In addition to STAT activation, M1 and M2 polarizing signals modulate the expression of inflammatory genes via differential activation of transcription factors and regulatory proteins, including NF-κB and SHIP1. In keeping with a critical role for Btk in macrophage polarization, we observed reduced levels of NF-κB p65 and Akt phosphorylation, as well as reduced induction of the M1 associated marker iNOS in Btk(−/−) macrophages in response to M1 polarizing stimuli. Additionally enhanced expression of SHIP1, a key negative regulator of macrophage polarisation, was observed in Btk(−/−) macrophages in response to M2 polarizing stimuli. Employing classic models of allergic M2 inflammation, treatment of Btk (−/−) mice with either Schistosoma mansoni eggs or chitin resulted in increased recruitment of M2 macrophages and induction of M2-associated genes. This demonstrates an enhanced M2 skew in the absence of Btk, thus promoting the development of allergic inflammation

Global warming and recurrent mass bleaching of corals

During 2015–2016, record temperatures triggered a pan-tropical episode of coral bleaching, the third global-scale event since mass bleaching was first documented in the 1980s. Here we examine how and why the severity of recurrent major bleaching events has varied at multiple scales, using aerial and underwater surveys of Australian reefs combined with satellite-derived sea surface temperatures. The distinctive geographic footprints of recurrent bleaching on the Great Barrier Reef in 1998, 2002 and 2016 were determined by the spatial pattern of sea temperatures in each year. Water quality and fishing pressure had minimal effect on the unprecedented bleaching in 2016, suggesting that local protection of reefs affords little or no resistance to extreme heat. Similarly, past exposure to bleaching in 1998 and 2002 did not lessen the severity of bleaching in 2016. Consequently, immediate global action to curb future warming is essential to secure a future for coral reefs

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

AbstractBackgroundThe genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder.MethodsWe analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures.ResultsThe SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10–9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10–9).ConclusionsThis large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression

Quasi-periodic acceleration of electrons by a plasmoid-driven shock in the solar atmosphere

Cosmic rays and solar energetic particles may be accelerated to relativistic energies by shock waves in astrophysical plasmas. On the Sun, shocks and particle acceleration are often associated with the eruption of magnetized plasmoids, called coronal mass ejections (CMEs). However, the physical relationship between CMEs and shock particle acceleration is not well understood. Here, we use extreme ultraviolet, radio and white-light imaging of a solar eruptive event on 22 September 2011 to show that a CME-induced shock (Alfvén Mach number 2:4+0:7 -0:8) was coincident with a coronal wave and an intense metric radio burst generated by intermittent acceleration of electrons to kinetic energies of 2{46 keV (0.1{0.4 c). Our observations show that plasmoid-driven quasi-perpendicular shocks are capable of producing quasi-periodic acceleration of electrons, an effect consistent with a turbulent or rippled plasma shock surface