Profiling of Canonical and Non-Traditional Cytokine Levels in Interferon-β-Treated Relapsing-Remitting-Multiple Sclerosis Patients

BACKGROUND: Multiple sclerosis (MS) is a chronic, progressive autoimmune disease of the central nervous system in which inflammation plays a key role in the induction, development, and progression. Most of the MS patients present with relapsing-remitting (RR) form, characterized by flare-ups followed by periods of recovery. Many inflammatory and anti-inflammatory cytokines have been proposed as backers in MS pathogenesis, and the balance between these differing cytokines can regulate MS severity. Interferon (IFN)-β, a current disease-modifying therapy for MS, has demonstrated beneficial effects in reducing disease severity in MS patients. However, its immunoregulatory and anti-inflammatory actions in MS are not wholly understood. The aim of the study was to define, in clinically stable patients with RR-MS, the serum concentration of several cytokines, canonical or not, and their modulation by IFN-β therapy. METHODS: Relapsing-remitting-MS patients were enrolled and diagnosed according to revised Mc Donald Diagnostic Criteria. A set of cytokines [including non-canonical neurotransmitter acetylcholine (ACh) and adipokines] and B-cell differentiation molecules, as potential biomarkers, were evaluated in 30 non-treated RR-MS patients compared to 30 IFN-β-treated MS patients and 30 age, gender, and body mass index-matched healthy controls (HC). RESULTS: Naïve MS patients showed significantly higher levels of interleukin (IL)-1β, IL-12/IL-23p40, IL-18, high-mobility group box protein-1, and IL-18 binding protein (IL-18BP) than MS-treated patients (p < 0.001 for all) and HC (p < 0.01). IFN-β therapy has significantly downmodulated IL-1β, IL-12/IL-23p40, IL-18 to normal levels (p < 0.001), whereas it has decreased IL-18BP (p < 0.001). ACh was significantly higher in the IFN-β-treated than HC and non-treated MS patients (p < 0.001). No significant differences were observed either in adipokines concentration or in B-cell-associated molecules among the three study groups. CONCLUSION: Although more experimental evidence are required, we speculate that the efficacy of treatment of MS with IFN-β is mediated, at least in part, by its ability to work on several levels to slow down the disease progression. Proposed actions include the modulation of IL-1-inflammasome axis and modulation of ACh, B-cell activating factor/a proliferation-inducing ligand system, and several adipokines

Chlamydia Pneumoniae CdsL Regulates CdsN ATPase Activity, and Disruption with a Peptide Mimetic Prevents Bacterial Invasion

Chlamydiae are obligate intracellular pathogens that likely require type III secretion (T3S) to invade cells and replicate intracellularly within a cytoplasmic vacuole called an inclusion body. Chlamydia pneumoniae possess a YscL ortholog, CdsL, that has been shown to interact with the T3S ATPase (CdsN). In this report we demonstrate that CdsL down-regulates CdsN enzymatic activity in a dose-dependent manner. Using Pepscan epitope mapping we identified two separate binding domains to which CdsL binds viz. CdsN221–229 and CdsN265–270. We confirmed the binding domains using a pull-down assay and showed that GST–CdsN221–270, which encompasses these peptides, co-purified with His–CdsL. Next, we used orthology modeling based on the crystal structure of a T3S ATPase ortholog from Escherichia coli, EscN, to map the binding domains on the predicted 3D structure of CdsN. The CdsL binding domains mapped to the catalytic domain of the ATPase, one in the central channel of the ATPase hexamer and one on the outer face. Since peptide mimetics have been used to disrupt essential protein interactions of the chlamydial T3S system and inhibit T3S-mediated invasion of HeLa cells, we hypothesized that if CdsL–CdsN binding is essential for regulating T3S then a CdsN peptide mimetic could be used to potentially block T3S and chlamydial invasion. Treatment of elementary body with a CdsN peptide mimetic inhibited C. pneumoniae invasion into HeLa cells in a dose-dependent fashion. This report represents the first use of Pepscan technology to identify binding domains for specific T3S proteins viz. CdsL on the ATPase, CdsN, and demonstrates that peptide mimetics can be used as anti-virulence factors to block bacterial invasion

Narratives from the road to social justice in PETE: teacher educator perspectives

Developing teacher education programmes founded upon principles of critical pedagogy and social justice has become increasingly difficult in the current neoliberal climate of higher education. In this article, we adopt a narrative approach to illuminate some of the dilemmas which advocates of education for social justice face and to reflect upon how pedagogy for inclusion in the field of physical education (PE) teacher education (PETE) is defined and practiced. As a professional group, teacher educators seem largely hesitant to expose themselves to the researcher's gaze, which is problematic if we expect preservice teachers to engage in messy, biographical reflexivity with regard to their own teaching practice. By engaging in self- and collective biographical story sharing about ‘our’ teacher educator struggles in England and Norway, we hope that the reader can identify ‘her/his’ struggles in the narratives about power and domination, and the spaces of opportunity in between

Performance of First Pacemaker to Use Smart Device App for Remote Monitoring

BACKGROUND: High adherence to remote monitoring (RM) in pacemaker (PM) patients improves outcomes; however, adherence remains suboptimal. Bluetooth low-energy (BLE) technology in newer-generation PMs enables communication directly with patient-owned smart devices using an app without a bedside console. OBJECTIVE: To evaluate the success rate of scheduled RM transmissions using the app compared to other RM methods. METHODS: The BlueSync Field Evaluation was a prospective, international cohort evaluation, measuring the success rate of scheduled RM transmissions using a BLE PM or cardiac resynchronization therapy PM coupled with the MyCareLink Heart app. App transmission success was compared to 3 historical “control” groups from the Medtronic de-identified CareLink database: (1) PM patients with manual communication using a wand with a bedside console (PM manual transmission), (2) PM patients with wireless automatic communication with the bedside console (PM wireless); (3) defibrillator patients with similar automatic communication (defibrillator wireless). RESULTS: Among 245 patients enrolled (age 64.8±15.6 years, 58.4% men), 953 transmissions were scheduled through 12 months, of which 902 (94.6%) were successfully completed. In comparison, transmission success rates were 56.3% for PM manual transmission patients, 77.0% for PM wireless patients, and 87.1% for defibrillator wireless patients. Transmission success with the app was superior across matched cohorts based on age, sex, and device type (single vs dual vs triple chamber). CONCLUSION: The success rate of scheduled RM transmissions was higher among patients using the smart device app compared to patients using traditional RM using bedside consoles. This novel technology may improve patient engagement and adherence to RM

Critical Media Literacy in the Time of Lies

The result of a consistent and total substitution of lies for factual truth is not that the lie will now be accepted as truth and the truth be defamed as a lie, but that the sense by which we take our bearings in the real world – and the category of truth versus falsehood is among the mental means to this end – is being destroyed. arendt, 1973, p. 14 … But most people use social media not to unite, not to open their horizons wider, but on the contrary, to cut themselves a comfort zone wher

Hick-Hop, Dirt Roads, Camouflage, Lift-Kit Trucks and John Deere: Rural White Working Class Pride

Presentation given at the International Critical Media Literacy Conference

First optical space debris detection campaign in Italy

In April 2002 the first dedicated observations of space debris in Italy have been performed by the Group of Astrodynamics of the University of Rome "La Sapienza". The campaign was accomplished using one of the Campo Catino Astronomical Observatory telescopes. In the paper the campaign is described and the first results are presented. (C) 2004 COSPAR. Published by Elsevier Ltd. All rights reserved

Backwoods Boys and their Hick-Hop and Indigenous Hip-Hop Culture

This presentation discusses the manifestations of White Working Class Pride through the analysis of Hick-Hop (Rural Rap) music. The historical development of Hick-Hop music and its connections to Hip-Hop will be analyzed. There will be an examination of representative examples of Hick-Hop including Bubba Sparks, Cypress Spring, The Lacs and Jawga Boyz to demonstrate the characteristics of Hick-Hop, white-pride, and the politics of working class empowerment. (Reynolds) The purpose of this presentation is to capture how cultural forms and activities of several Indigenous Hip-Hop artists in Canada formulate a revolutionary pedagogical project dedicated to self-empowerment, to subverting settler colonialism, and to building a social order free from hate, hostility, and inequality. The study is a qualitative case study focusing on the cultural practices and activities generated by several leading Hip-Hop Indigenous intellectuals in Canada, including Ostwelve, Dakota Bear, Joey Stylez, and Jb the First Lady. The chief source of data comes a documentary produced on Indigenous Hip-Hop culture during the winter of 2020. In total, almost 16 hours of footage was generated from workshops, rallies and protests, artistic performances, and community-based activities launched by several Indigenous Hip-Hop artists and community members. (Porfilio