CpG oligodeoxynucleotide stimulates production of anti-neutrophil cytoplasmic antibodies in ANCA associated vasculitis

Background Wegener's Granulomatosis and Microscopic Polyangiitis are life-threatening systemic necrotizing vasculitides of unknown aetiology. The appearance of circulating antibodies to neutrophil cytoplasmic antigens (ANCA) is strongly associated with the development of the disease. A link between infection and disease has long been suspected, and the appearance of ANCA antibodies has been reported following bacterial and viral infections. The depletion of circulating B cells with monoclonal antibody therapy can induce remission, and this observation suggests a pathogenic role for B cells in this disease. As bacterial DNA is known to induce B cell proliferation and antibody production via TLR-9 stimulation, we have explored the possibility that unmethylated CpG oligodeoxynucleotide, as found in bacterial and viral DNA, may play a role in stimulating circulating autoreactive B cells to produce ANCA in patients with vasculitis. Results We have confirmed that unmethylated CpG oligonucleotide is a potent stimulator of antibody production by PBMC in vitro. The stimulation of PBMC with CpG oligonucleutides resulted in the production of similar amounts of IgG in both ANCA+ patients and normal controls. In spite of this, PR3 ANCA+ patients synthesised significantly higher amount of IgG ANCA than normal controls. In MPO ANCA+ patients, there was a tendency for patients to produce higher amount of ANCA than controls, however, the difference did not reach significance. Furthermore, we were able to detect circulating MPO-reactive B cells by ELISpot assay from the peripheral blood of 2 MPO+ ANCA vasculitis patients. Together, this indicates that circulating anti-neutrophil autoreactive B cells are present in ANCA+ vasculitis patients, and they are capable of producing antibodies in response to CpG stimulation. Of note, CpG also induced the production of the relevant autoantibodies in patients with other types of autoimmune diseases. Conclusion Circulating ANCA autoreactive B cells are present in patients with ANCA+ vasculitis. The production of ANCA from these cells in response to unmethylated CpG stimulation lead us to propose that stimulation of these cells by immunostimulatory DNA sequences such as CpG oligodeoxynucleotide during infection may provide a link between infection and ANCA associated vasculitis. This phenomenon may also apply to other antibody mediated autoimmune diseases.Plinio R Hurtado, Lisa Jeffs, Jodie Nitschke, Mittal Patel, Ghafar Sarvestani, John Cassidy, Pravin Hissaria, David Gillis and Chen Au Pe

Microstructure dependence of performance degradation for intermediate temperature solid oxide fuel cells based on the metallic catalyst infiltrated La- and Ca-doped SrTiO3 anode support

The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) for the Fuel Cells and Hydrogen Joint Technology Initiative under grant agreement No. 256730 and Energy Technology Partnership (ETP). C. Ni also would like to thank the support from the Natural Science Foundation of China (NSFC, 51702264) Fundamental Research Funds for the Central Universities (XDJK2017B033) and Research Funding of Southwest University (SWU117019).Anode-supported solid oxide fuel cells with the configuration of the La0.2Sr0.25Ca0.45TiO3 (LSCTA-) anode, YSZ electrolyte and La0.8Sr0.2Co0.2Fe0.8O3 (LSCF)-YSZ cathode were fabricated using tape casting and co-sintering techniques followed by pre-reduction and impregnation. In order to improve the performance, the active anodes were prepared via the wet impregnation of metallic catalysts (Ni or Ni-Fe solution). The impregnation of 3 wt% nickel significantly improved the fuel cell performance from 43 mW cm-2 for the bare LSCTA- anode to 112 mW cm-2 for the Ni-LSCTA- anode at 700 °C in humidified hydrogen containing 3 vol% H2O. More interestingly, the substitution of 25 wt% Fe to Ni further enhances the power density by a factor of 1.5, compared to the Ni-impregnated cell. The cell infiltrated with Ni-Fe solid solution shows a slower degradation than the other two cells after the first 20 h period. High-resolution back-scattered electron (BSE) and transmission electron microscopy (TEM) images performed on the cross section of the impregnated anodes with time after ion beam preparation show that the sintering of the catalyst particles on the scaffold surface and the interaction between backbone and catalyst are the predominant contributions for the degradation of cell performance.PostprintPeer reviewe

Neurocognitive Considerations and Impacts in Chronic Migraines

Migraine, characterized by moderate-to-severe headache, may arise from neurological, psychological, orthopedic, metabolic, or endocrine origins. Pain associated with migraine, while commonly cited as the primary patient concern, only represents a small portion of short- and long-term effects caused by the condition. Many presenting cases include neuromuscular dysfunction, increased neuronal firing, inflammation, and cortical spreading depression. These effects can induce multiple symptoms such as pain, aura, brain fog, confusion, hangover, multiple hypersensitivities, and decreased memory capacity. These effects and symptoms can lead to neurocognitive and neuropsychological deficiencies in many patients. This study aims to investigate the relationship between migraines and neurocognitive function

New partnerships for co-delivery of the 2030 agenda for sustainable development

Partnerships have become a corner stone of contemporary research that recognizes working across disciplines and co-production with intended users as essential to enabling sustainable resilience-building. Furthermore, research that addresses sustainable development challenges brings an urgent need to reflect on the ways that partnerships are supported, and for the disaster risk management and resilience communities, efforts to support realization of the wider 2030 Agenda for sustainable development bring particular pressures. In November 2019, the UK Disasters Research Group (DRG) brought together a number of key stakeholders focused on disaster risk, resilience, and sustainability research relevant to Official Development Assistance to consider how fit for purpose existing partnership models are for the pace of change required to deliver the priorities of the wider 2030 Agenda. Participants were invited to discuss how research partnerships across three levels (individual and project-based; national and institutional; and international) could be improved based on elements that facilitate robust partnerships and learning from aspects that hinder them. From the discussions, participants emphasized the importance of effective communication mechanisms in building partnerships, co-designing projects, and establishing shared objectives. Enhanced approaches to addressing equitable partnerships and funding more substantive timelines will be key to responding to the challenges of the 2030 Agenda

Prospectus, May 7, 1971

PREPAREDNESS PROGRAM GIVES SECOND CHANCE; VIC Helps To Rehabilitate Youth; Nurses, Hygienists In Health Week ; One Way or Two?; Student Deferment May End; One Man Band; Bull Sheet: Elections, Game Week, Sisters, Hot Line, Wit n\u27 Wisdom, Counselor Appts., Tau Epsilon, Voting, New Paperbacks, Anti War Activities, IOC, Vets Meeting, About Drugs, Need Help, Book Depository, LRC File, Poncho Pilot; Parkland Belts Walbash Twice; P.C. Board Holds Elections-- Consider Nepotism Policy; PC Faculty Art Exhibit; Know Your Candidate: Student Government Elections, Will They Pass or Fail?; David A. Friedmann, President; Robert D. Bales, President; John Stuckey, Vice President; Bob Hilton, Treasurer; Diane Topping, Secretary; Becky Terrell, Convocations; Terry Cassidy, Campus Organizationshttps://spark.parkland.edu/prospectus_1971/1007/thumbnail.jp

The Cognitive Ageing, Nutrition and Neurogenesis trial: Design and progress

Introduction: Cohort studies indicate that long-chain n-3 polyunsaturated fatty acids and flavonoids may improve cognition and reduce dementia risk. The neuroprotective effects of these dietary components indicate that they are likely to be additive and potentially synergistic. Methods: The Cognitive Ageing, Nutrition and Neurogenesis trial hypothesizes that an intervention comprising long-chain n-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid) and cocoa flavan-3-ols (n-3 FLAV) will mitigate the cognitive decline anticipated to naturally occur over 1 year in older adults with mild cognitive impairment or subjective memory impairment. A double-blinded, placebo-controlled parallel design is used. Two hundred fifty-nine adults (aged ≥55 years) with mild cognitive impairment or subjective memory impairment were recruited and randomized to a control or n-3 FLAV group (1.5 g docosahexaenoic acid + eicosapentaenoic acid and 500 mg n-3 FLAV daily) for 12 months. Cognitive performance was measured three times over the 1-year intervention, at 0 (baseline), 3, and 12 months. The primary end point is hippocampus-sensitive cognitive function (e.g., number of false-positives on the Picture Recognition Task of the Cognitive Drug Research test battery). Secondary outcomes include additional cognitive measures, brain atrophy and blood flow (assessed by magnetic resonance imaging), vascular function, circulating biomarkers of cardiovascular and cognitive health, gut microflora speciation and metabolism, red blood cell fatty acid status, and urine flavan-3-ol metabolites. The intervention arms were matched for sex and apolipoprotein E4 status to allow retrospective exploratory analysis of the impact of these variables on response to intervention.  Results: Screening began in 2015, with all baseline visits completed in March 2017. The intervention was finished in March 2018.  Discussion: Cognitive Ageing, Nutrition and Neurogenesis aims to identify an effective diet-based intervention to prevent or delay cognitive impairment in cognitively at-risk individuals, which could ultimately contribute to a reduced population burden of dementia

Frontiers in Pigment Cell and Melanoma Research

We identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. We describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. We focus on four themes: (1) clinical melanoma research, (2) basic melanoma research, (3) clinical dermatology, and (4) basic pigment cell research, with the goal of outlining current highlights, challenges, and frontiers associated with pigmentation and melanocyte biology. Significantly, this document encapsulates important advances in melanocyte and melanoma research including emerging frontiers in melanoma immunotherapy, medical and surgical oncology, dermatology, vitiligo, albinism, genomics and systems biology, epidemiology, pigment biophysics and chemistry, and evolution

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Comparison of Inappropriate Shocks and Other Health Outcomes Between Single- and Dual-Chamber Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death: Results From the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter-Defibrillators

BACKGROUND: In US clinical practice, many patients who undergo placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death receive dual-chamber devices. The superiority of dual-chamber over single-chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single- and dual-chamber ICDs for primary prevention. METHODS AND RESULTS: We identified patients receiving a single- or dual-chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health delivery systems in the Longitudinal Study of Implantable Cardioverter-Defibrillators from 2006 to 2009. The primary outcome was time to first inappropriate shock. ICD shocks were adjudicated for appropriateness. Other outcomes included all-cause hospitalization, heart failure hospitalization, and death. Patient, clinician, and hospital-level factors were accounted for using propensity score weighting methods. Among 1042 patients without pacing indications, 54.0% (n=563) received a single-chamber device and 46.0% (n=479) received a dual-chamber device. In a propensity-weighted analysis, device type was not significantly associated with inappropriate shock (hazard ratio, 0.91; 95% confidence interval, 0.59-1.38 [P=0.65]), all-cause hospitalization (hazard ratio, 1.03; 95% confidence interval, 0.87-1.21 [P=0.76]), heart failure hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.72-1.21 [P=0.59]), or death (hazard ratio, 1.19; 95% confidence interval, 0.93-1.53 [P=0.17]). CONCLUSIONS: Among patients who received an ICD for primary prevention without indications for pacing, dual-chamber devices were not associated with lower risk of inappropriate shock or differences in hospitalization or death compared with single-chamber devices. This study does not justify the use of dual-chamber devices to minimize inappropriate shocks