Carotid Artery Reactivity Predicts Events in Peripheral Arterial Disease Patients.

OBJECTIVE: Patients with peripheral arterial disease (PAD) have increased risk on future cerebro- and cardiovascular events. Our aim was to examine whether carotid artery reactivity (CAR; a novel, simple procedure to examine endothelial function) predicts cardiovascular events in PAD patients. BACKGROUND: Increased risk for future cardiovascular events in PAD patients is likely related to endothelial dysfunction, highlighting the necessity for simple assessment of endothelial function. METHODS: A total of 172 PAD patients (68 ± 10 years, 67% male) underwent the CAR, which involves ultrasound measurement of carotid artery diameter during sympathetic stimulation produced by 90-second hand immersion in 4°C ice-water (ie, cold pressor test). CAR-responses were dichotomized into carotid constriction or dilation. We recorded cardiac and cerebrovascular events, mortality, and clinical progression to percutaneous transluminal angioplasty or loss of patency during 12-month follow-up. RESULTS: Eighty-two PAD patients demonstrated carotid constriction and 90 patients demonstrated dilation. PAD patients with carotid constriction showed more cardiovascular events compared to patients with dilation (Kaplan-Meier Log rank; P < 0.05). Cox proportional hazard models showed that patients with carotid constriction continued to show higher risk for cardiovascular events [hazard ratio: 4.1; 95% confidence interval (CI), 1.3-12.5] and clinical progression (hazard ratio: 2.0; 95% CI, 1.2-3.3), even after adjustment for other risk factors. Ankle brachial pressure index and carotid intima-medial thickness alone did not predict (cardiovascular) event or improve risk assessment beyond that provided by CAR. CONCLUSION: Carotid vasoconstriction identifies PAD patients with a 4-fold increased risk for future cardiovascular events and 2-fold increased risk for clinical deterioration. CAR provides a simple, novel strategy to predict cardiovascular events and progression in PAD patients. CLINICAL TRIAL REGISTRATION: www.trialregister.nl/trialreg/index.asp, NTR-4117

Near polygons and Fischer spaces

In this paper we exploit the relations between near polygons with lines of size 3 and Fischer spaces to classify near hexagons with quads and with lines of size three. We also construct some infinite families of near polygons

Linking Power Doppler Ultrasound to the Presence of Th17 Cells in the Rheumatoid Arthritis Joint

Power Doppler ultrasound (PDUS) is increasingly used to assess synovitis in Rheumatoid Arthritis (RA). Prior studies have shown correlations between PDUS scores and vessel counts, but relationships with T cell immunopathology have not been described.PBMC were isolated from healthy controls (HC) or RA patients and stimulated ex vivo with PMA and ionomycin for 3 hours in the presence of Golgistop. Paired synovial fluid (SF) or synovial tissue (ST) were analysed where available. Intracellular expression of IL-17, IFNgamma, and TNFalpha by CD4+ T cells was determined by flow cytometry. Synovial blood flow was evaluated by PDUS signal at the knees, wrists and metacarpophalangeal joints of RA patients. Serum, SF and fibroblast culture supernatant levels of vascular endothelial growth factor-A (VEGF-A) were measured by ELISA. The frequency of IL17+IFNgamma-CD4+ T cells (Th17 cells) was significantly elevated in peripheral blood (PB) from RA patients vs. HC (median (IQR) 0.5 (0.28-1.59)% vs. 0.32 (0.21-0.54)%, p = 0.005). Th17 cells were further enriched (mean 6.6-fold increase) in RA SF relative to RA PB. Patients with active disease had a higher percentage of IL-17+ T cells in ST than patients in remission, suggesting a possible role for Th17 cells in active synovitis in RA. Indeed, the percentage of Th17 cells, but not Th1, in SF positively correlated with CRP (r = 0.51, p = 0.04) and local PDUS-defined synovitis (r = 0.61, p = 0.002). Furthermore, patients with high levels of IL-17+CD4+ T cells in SF had increased levels of the angiogenic factor VEGF-A in SF. Finally, IL-17, but not IFNgamma, increased VEGF-A production by RA synovial fibroblasts in vitro.Our data demonstrate a link between the presence of pro-inflammatory Th17 cells in SF and local PDUS scores, and offer a novel immunological explanation for the observation that rapid joint damage progression occurs in patients with persistent positive PDUS signal

Risk factors for acute respiratory tract infections in general practitioner patients in The Netherlands: a case-control study

<p>Abstract</p> <p>Background</p> <p>Acute respiratory tract infections (ARTI) are an important public health problem. Improved identification of risk factors might enable targeted intervention. Therefore we carried out a case-control study with the aim of identifying environmental risk factors for ARTI consultations in the Dutch general population.</p> <p>Methods</p> <p>A subset of patients visiting their GP in the period of 2000–2003 with an ARTI (cases) and age-matched controls (visiting for other complaints) were included in a case-control study. They were asked to complete a questionnaire about potential risk factors. Conditional logistic regression was used to calculate odds ratio's (OR) and 95% confidence intervals (CI) to estimate the independent effect of potential risk factors.</p> <p>Results</p> <p>A total of 493 matched pairs of case and control subjects were enrolled. Exposure to persons with respiratory complaints, both inside and outside the household, was found to be an independent risk factor for visiting a GP with an ARTI (respectively OR_adj= 1.9 and OR_adj= 3.7). Participants exposed to dampness or mould at home (OR_adj=0.5) were significantly less likely to visit their GP. In accordance with the general risk of consultations for ARTI, participants with a laboratory-confirmed ARTI who were exposed to persons with respiratory complaints outside the household were also significantly more likely to visit their GP (OR_adj=2.5).</p> <p>Conclusion</p> <p>This study confirmed that heterogeneity in the general population as well as in pathogens causing ARTI makes it complicated to detect associations between potential risk factors and respiratory infections. Whereas it may be difficult to intervene on the risk posed by exposure to persons with respiratory complaints, transmission of ARTI in the general population might be reduced by improved hygienic conditions.</p

Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor

Objective: The objective of this study was to aggregate data for the first genomewide association study meta-analysis of cluster headache, to identify genetic risk variants, and gain biological insights. Methods: A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse-variance genomewide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans-ancestry meta-analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome-wide association, fine-mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses. Results: The estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta-analysis, and one additional locus in the trans-ethnic meta-analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine. Interpretation: This first genomewide association study meta-analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor. ANN NEUROL 2023

Rheumatoid arthritis and the role of oral bacteria

Rheumatoid arthritis (RA) and periodontal disease (PD) have shown similar physiopathologic mechanisms such as chronic inflammation with adjacent bone resorption in an immunogenetically susceptible host; however, PD has a well-recognized bacterial etiology while the cause of RA is unclear. Some reports have indicated that an infectious agent in a susceptible host could be one possible trigger factor for RA, and it has been suggested that oral microorganisms, specialty periodontal bacteria could be the infectious agent (mainly Porphyromonas gingivalis). It has been reported that PD is more frequent and more severe in patients with RA, suggesting a positive association between both diseases. There have been reports regarding the detection of antibodies against periodontal bacteria while other studies have identified periodontal bacterial DNA in serum and synovial fluid of RA patients and have explored the possible pathways of transport of periodontal bacterial DNA. In conclusion, there is no question that RA and PD have pathologic features in common and there is strong evidence of an association between both diseases, but further studies, including experimental models, are needed to demonstrate the arthritogenicity of oral microorganisms

Exploring data provenance in handwritten text recognition infrastructure:Sharing and reusing ground truth data, referencing models, and acknowledging contributions. Starting the conversation on how we could get it done

This paper discusses best practices for sharing and reusing Ground Truth in Handwritten Text Recognition infrastructures, and ways to reference and acknowledge contributions to the creation and enrichment of data within these Machine Learning systems. We discuss how one can publish Ground Truth data in a repository and, subsequently, inform others. Furthermore, we suggest appropriate citation methods for HTR data, models, and contributions made by volunteers. Moreover, when using digitised sources (digital facsimiles), it becomes increasingly important to distinguish between the physical object and the digital collection. These topics all relate to the proper acknowledgement of labour put into digitising, transcribing, and sharing Ground Truth HTR data. This also points to broader issues surrounding the use of Machine Learning in archival and library contexts, and how the community should begin toacknowledge and record both contributions and data provenance

Exploring Data Provenance in Handwritten Text Recognition Infrastructure: Sharing and Reusing Ground Truth Data, Referencing Models, and Acknowledging Contributions. Starting the Conversation on How We Could Get It Done

This paper discusses best practices for sharing and reusing Ground Truth in Handwritten Text Recognition infrastructures, as well as ways to reference and acknowledge contributions to the creation and enrichment of data within these systems. We discuss how one can place Ground Truth data in a repository and, subsequently, inform others through HTR-United. Furthermore, we want to suggest appropriate citation methods for ATR data, models, and contributions made by volunteers. Moreover, when using digitised sources (digital facsimiles), it becomes increasingly important to distinguish between the physical object and the digital collection. These topics all relate to the proper acknowledgement of labour put into digitising, transcribing, and sharing Ground Truth HTR data. This also points to broader issues surrounding the use of machine learning in archival and library contexts, and how the community should begin to acknowledge and record both contributions and data provenance