Induction of Tachykinin Production in Airway Epithelia in Response to Viral Infection

The tachykinins are implicated in neurogenic inflammation and the neuropeptide substance P in particular has been shown to be a proinflammatory mediator. A role for the tachykinins in host response to lung challenge has been previously demonstrated but has been focused predominantly on the release of the tachykinins from nerves innervating the lung. We have previously demonstrated the most dramatic phenotype described for the substance P encoding gene preprotachykinin-A (PPT-A) to date in controlling the host immune response to the murine gammaherpesvirus 68, in the lung.In this study we have utilised transgenic mice engineered to co-ordinately express the beta-galactosidase marker gene along with PPT-A to facilitate the tracking of PPT-A expression. Using a combination of these mice and conventional immunohistology we now demonstrate that PPT-A gene expression and substance P peptide are induced in cells of the respiratory tract including tracheal, bronchiolar and alveolar epithelial cells and macrophages after viral infection. This induction was observed 24h post infection, prior to observable inflammation and the expression of pro-inflammatory chemokines in this model. Induced expression of the PPT-A gene and peptide persisted in the lower respiratory tract through day 7 post infection.Non-neuronal PPT-A expression early after infection may have important clinical implications for the progression or management of lung disease or infection aside from the well characterised later involvement of the tachykinins during the inflammatory response

Serum Inflammatory Profile for the Discrimination of Clinical Subtypes in Parkinson's Disease

Background: Blood levels of immune markers have been proposed to discriminate patients with Parkinson's disease (PD) from controls. However, differences between clinical PD subgroups regarding these markers still need to be identified. Objective: To investigate whether clinical phenotypes can be predicted by the assessment of immune marker profiles in the serum of PD patients. Methods: Phenotypes of clinical PD from Tübingen, Germany (n = 145) and Toronto, Canada (n = 90) were defined regarding clinical subtype, disease onset, severity, and progression as well as presence of cognitive and/or autonomic dysfunction. A panel of serum immune markers was assessed using principal component analysis (PCA) and regression models to define the marker(s) that were associated with clinical phenotypes after adjusting for potential confounders. Findings of both centers were compared for validation. Further, a [18F] FEPPA-PET was performed in a group of patients with high and low values of candidate markers for the assessment of in vivo brain microglial activation. Results: Overall, serum immune markers did not cluster to define a pro/anti-inflammatory profile in PCA. Out of 25 markers only IL-12p40 showed a trend to discriminate between PD subgroups in both cohorts which could not be replicated by [18F] FEPPA-PET. Conclusions: Assessment of cytokines in serum does not reliably differentiate clinical PD subtypes. Accompanying subtype-irrelevant inflammation in PD, dual activity, and lack of specificity of the immune markers, the complex function of microglia, probable effects of treatment, disease stage, and progression on inflammation as well as current technical limitations may limit the usefulness of serum immune markers for the differentiation of subtypes

Inflammatory profile in LRRK2-associated prodromal and clinical PD

BACKGROUND There is evidence for a relevant role of inflammation in the pathogenesis of Parkinson's disease (PD). Mutations in the LRRK2 gene represent the most frequent genetic cause for autosomal dominant PD. LRRK2 is highly expressed in macrophages and microglia suggesting an involvement in inflammatory pathways. The objectives are to test (1) whether idiopathic PD and LRRK2-associated PD share common inflammatory pathways or present distinct profiles and (2) whether non-manifesting LRRK2 mutation carriers present with similar aspects of inflammatory profiles as seen in PD-affected patients. METHODS We assessed serum profiles of 23 immune-associated markers and the brain-derived neurotrophic factor in 534 individuals from the MJFF LRRK2 consortium. RESULTS A large proportion of inflammatory markers were gender-dependent. Both PD-affected cohorts showed increased levels of the pro-inflammatory marker fatty-acid-binding protein. Additionally, idiopathic PD but not LRRK2-associated PD patients showed increased levels of the pro-inflammatory marker interleukin-12-p40 as well as the anti-inflammatory species interleukin-10, brain-derived neurotrophic factor, and stem cell factor. Non-manifesting LRRK2 mutation carriers including those with prodromal characteristics of PD presented with control-like inflammatory profiles. CONCLUSIONS Concomitant inflammation seems to be associated with idiopathic and LRRK2-associated PD. Identifying PD patients in whom inflammatory processes play a major role in their pathophysiology might offer a new therapeutic window at least for a subgroup of patients. Since non-manifesting LRRK2 mutation carriers with symptoms of the prodromal phase of PD did not show inflammatory profiles, activation of the immune system seems not an early event in the disease cascade

Serum Inflammatory Profile for the Discrimination of Clinical Subtypes in Parkinson's Disease

Background: Blood levels of immune markers have been proposed to discriminate patients with Parkinson's disease (PD) from controls. However, differences between clinical PD subgroups regarding these markers still need to be identified.Objective: To investigate whether clinical phenotypes can be predicted by the assessment of immune marker profiles in the serum of PD patients.Methods: Phenotypes of clinical PD from Tübingen, Germany (n = 145) and Toronto, Canada (n = 90) were defined regarding clinical subtype, disease onset, severity, and progression as well as presence of cognitive and/or autonomic dysfunction. A panel of serum immune markers was assessed using principal component analysis (PCA) and regression models to define the marker(s) that were associated with clinical phenotypes after adjusting for potential confounders. Findings of both centers were compared for validation. Further, a [18F] FEPPA-PET was performed in a group of patients with high and low values of candidate markers for the assessment of in vivo brain microglial activation.Results: Overall, serum immune markers did not cluster to define a pro/anti-inflammatory profile in PCA. Out of 25 markers only IL-12p40 showed a trend to discriminate between PD subgroups in both cohorts which could not be replicated by [18F] FEPPA-PET.Conclusions: Assessment of cytokines in serum does not reliably differentiate clinical PD subtypes. Accompanying subtype-irrelevant inflammation in PD, dual activity, and lack of specificity of the immune markers, the complex function of microglia, probable effects of treatment, disease stage, and progression on inflammation as well as current technical limitations may limit the usefulness of serum immune markers for the differentiation of subtypes

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Improvisation: an empirical study on improvisational action

Para la sociología, que se ocupa del orden social y los modos de interacción, el tema de la improvisación constituye un campo de investigación emocionante. Sin embargo, solamente unos cuantos científicos sociales se han ocupado de esta forma de acción. El análisis de las acciones es a menudo realizado por las teorías clásicas de acción, por ejemplo, la teoría de Thomas Luckmann que se desarrolla en este artículo. Este trabajo pretende acercarse al tema de la improvisación y para ello se centrará en el teatro de improvisación, el cual, hasta el momento, apenas fue investigado por los científicos sociales. El artículo pretende investigar cómo se desarrollan las acciones improvisatorias y qué reglas posiblemente siguen. Particularmente se analizará una escena de teatro de improvisación con el método de teoría fundamentada, para así descubrir posibles categorías de acciones

Tiga är silver - Tala är guld : En kvalitativ studie om hur företag arbetar med frågor, kritik och feedback genom dialog i sociala medier

Sociala medier innebär både stora hot och möjligheter. Möjligheterna är större än någonsin för organisationer att integrera med sina intressenter och utifrån det bygga starka relationer. Samtidigt innebär den snabba spridning av information som kanalerna innebär ett hot för organisationer. Att rykten eller kritik uppstår och växer sig starka i sociala medier är en stor fara och utmaning för organisationer världen över. Ryktesspridning och konflikter kan motverkas genom att organisationen kommunicerar öppet och trovärdigt. I studien studeras hur företag arbetar med frågor, kritik och feedback genom dialog i sociala medier. Syftet med studien är att beskriva hur utvalda svenska företag arbetar med frågor, kritik och feedback genom dialog i sociala medier för att stärka sina kundrelationer. Studien besvarar följande frågeställningar: • Hur beskriver de utvalda företagen sitt arbete med frågor, kritik och feedback genom dialog i sociala medier? • Hur ser innehållet ut i företagens arbete med frågor, kritik och feedback genom dialog i sociala medier? Frågeställningarna besvarades med hjälp av en kvalitativ metod. Studien inleddes med att vi genomförda kvalitativa samtalsintervjuer med representanter för de utvalda svenska företagen Com Hem, TeliaSonera, Trygg-Hansa och Ving. I intervjuerna fick respondenterna möjlighet att beskriva företagets arbete med frågor, kritik och feedback. Därefter studerades innehållet i företagens kommunikation i sociala medier genom att vi genomförde kvalitativa innehållsanalyser i Twitter, Facebook och bloggosfären. Studiens resultat visar att sociala medier har blivit en etablerad kanal för företagens arbete med frågor, kritik och feedback. Företagen arbetar kontinuerligt med att besvara frågor, kritik och feedback, vilket ligger i linje med hur konflikter och osäkerhet hos intressenter bör hanteras. Det förekommer både likheter och skillnader mellan företagens arbete. Genomgående är arbetet inte är ett utryck av spontana infall utan grundar sig i en strategi. Företagen anpassar sig till omständigheterna i sociala medier och använder sig av personliga budskap. Överlag visar företagen på en förståelse för sociala mediers förutsättningar och utnyttjar möjligheterna till dialog. Hur aktiva företagen är i arbetet med frågor, kritik och feedback skiljer sig till viss del dem emellan. Det finns även skillnader i hur arbetet ser ut mellan de olika sociala medierna. Tonen i dialogen som företagen deltar i på Facebook och Twitter är mestadels positiv. I bloggosfären är företagens arbete framförallt inriktat på att kommunicera med missnöjda kunder. Ett problem med arbetet i sociala medier är att det är svårt att utvärdera om det faktiskt påverkar relationen företag och kunder