Complement and humoral adaptive immunity in the human choroid plexus: roles for stromal concretions, basement membranes, and epithelium

The choroid plexus (CP) provides a barrier to entry of toxic molecules from the blood into the brain and transports vital molecules into the cerebrospinal fluid. While a great deal is known about CP physiology, relatively little is known about its immunology. Here, we show immunohistochemical data that help define the role of the CP in innate and adaptive humoral immunity. The results show that complement, in the form of C1q, C3d, C9, or C9neo, is preferentially deposited in stromal concretions. In contrast, immunoglobulin (Ig) G (IgG) and IgA are more often found in CP epithelial cells, and IgM is found in either locale. C4d, IgD, and IgE are rarely, if ever, seen in the CP. In multiple sclerosis CP, basement membrane C9 or stromal IgA patterns were common but were not specific for the disease. These findings indicate that the CP may orchestrate the clearance of complement, particularly by deposition in its concretions, IgA and IgG preferentially via its epithelium, and IgM by either mechanism

Localization of sucrose synthase in developing seed and siliques of Arabidopsis thaliana reveals diverse roles for SUS during development

This study investigated the roles of sucrose synthase (SUS) in developing seeds and siliques of Arabidopsis thaliana. Enzyme activity assays showed that SUS activity was highest in developing whole siliques and young rosette leaves compared with other tissues including mature leaves, stems, and flowers. Surprisingly, quantitative PCR analyses revealed little correlation between SUS activity and transcript expression, which indicated the importance of examining the role of SUS at the protein level. Therefore, immunolocalization was performed over a developmental time course to determine the previously unreported cellular localization of SUS in Arabidopsis seed and silique tissues. At 3 d and 10 d after flowering (daf), SUS protein localized to the silique wall, seed coat, funiculus, and endosperm. By 13 daf, SUS protein was detected in the embryo and aleurone layer, but was absent from the seed coat and funiculus. Starch grains were also present in the seed coat at 3 and 10 daf, but were absent at 13 daf. Co-localization of SUS protein and starch grains in the seed coat at 3 and 10 daf indicates that SUS may be involved in temporary starch deposition during the early stages of seed development, whilst in the later stages SUS metabolizes sucrose in the embryo and cotyledon. Within the silique wall, SUS localized specifically to the companion cells, indicating that SUS activity may be required to provide energy for phloem transport activities in the silique wall. The results highlight the diverse roles that SUS may play during the development of silique and seed in Arabidopsis

Patient Acceptance of Noninvasive and Invasive Coronary Angiography

BACKGROUND: Noninvasive angiography using multislice computed tomography (MSCT) is superior to magnetic resonance imaging (MRI) for detection of coronary stenoses. We compared patient acceptance of these two noninvasive diagnostic tests and invasive conventional coronary angiography (Angio). METHODS AND FINDINGS: A total of 111 consecutive patients with suspected coronary artery disease underwent MSCT, MRI, and Angio. Subsequently, patient acceptance of the three tests was evaluated with questionnaires in all patients. The main acceptance variables were preparation and information prior to the test, degree of concern, comfort, degree of helplessness, pain (on visual analog scales), willingness to undergo the test again, and overall satisfaction. Preparation for each test was not rated significantly differently, whereas patients were significantly more concerned about Angio than the two noninvasive tests (p<0.001). No pain during MSCT, MRI, and Angio as assessed on visual analog scales (0 to 100) was reported by 99, 93, and 31 patients, respectively. Among the 82 patients who felt pain during at least one procedure, both CT (0.9±4.5) and MRI (5.2±16.6) were significantly less painful than Angio (24.6±23.4, both p<0.001). MSCT was considered significantly more comfortable (1.49±0.64) than MRI (1.75±0.81, p<0.001). In both the no-revascularization (55 patients) and the revascularization group (56 patients), the majority of the patients (73 and 71%) would prefer MSCT to MRI and Angio for future imaging of the coronary arteries. None of the patients indicated to be unwilling to undergo MSCT again. The major advantages patients attributed to MSCT were its fast, uncomplicated, noninvasive, and painless nature. CONCLUSIONS: Noninvasive coronary angiography with MSCT is considered more comfortable than MRI and both MSCT and MRI are less painful than Angio. Patient preference for MSCT might tip the scales in favor of this test provided that the diagnostic accuracy of MSCT can be shown to be high enough for clinical application

Prediction model to estimate presence of coronary artery disease: retrospective pooled analysis of existing cohorts

Objectives To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations

Generic acquisition protocol for quantitative MRI of the spinal cord

Quantitative spinal cord (SC) magnetic resonance imaging (MRI) presents many challenges, including a lack of standardized imaging protocols. Here we present a prospectively harmonized quantitative MRI protocol, which we refer to as the spine generic protocol, for users of 3T MRI systems from the three main manufacturers: GE, Philips and Siemens. The protocol provides guidance for assessing SC macrostructural and microstructural integrity: T1-weighted and T2-weighted imaging for SC cross-sectional area computation, multi-echo gradient echo for gray matter cross-sectional area, and magnetization transfer and diffusion weighted imaging for assessing white matter microstructure. In a companion paper from the same authors, the spine generic protocol was used to acquire data across 42 centers in 260 healthy subjects. The key details of the spine generic protocol are also available in an open-access document that can be found at https://github.com/spine-generic/protocols. The protocol will serve as a starting point for researchers and clinicians implementing new SC imaging initiatives so that, in the future, inclusion of the SC in neuroimaging protocols will be more common. The protocol could be implemented by any trained MR technician or by a researcher/clinician familiar with MRI acquisition

Open-access quantitative MRI data of the spinal cord and reproducibility across participants, sites and manufacturers

In a companion paper by Cohen-Adad et al. we introduce the spine generic quantitative MRI protocol that provides valuable metrics for assessing spinal cord macrostructural and microstructural integrity. This protocol was used to acquire a single subject dataset across 19 centers and a multi-subject dataset across 42 centers (for a total of 260 participants), spanning the three main MRI manufacturers: GE, Philips and Siemens. Both datasets are publicly available via git-annex. Data were analysed using the Spinal Cord Toolbox to produce normative values as well as inter/intra-site and inter/intra-manufacturer statistics. Reproducibility for the spine generic protocol was high across sites and manufacturers, with an average inter-site coefficient of variation of less than 5% for all the metrics. Full documentation and results can be found at https://spine-generic.rtfd.io/. The datasets and analysis pipeline will help pave the way towards accessible and reproducible quantitative MRI in the spinal cord

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: Meta-analysis of individual patient data

Objective To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. Design Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. Data sources Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. Eligibility criteria for selecting studies Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2 72 or 3 72 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. Results Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P&lt;0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P&lt;0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). Conclusions In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. Systematic review registration PROSPERO CRD42012002780