Forming nacreous layer of the shells of the bivalves Atrina rigida and Pinctada margaritifera: An environmental- and cryo-scanning electron microscopy study

International audienceA key to understanding control over mineral formation in mollusk shells is the microenvironment inside the pre-formed 3-dimensional organic matrix framework where mineral forms. Much of what is known about nacre formation is from observations of the mature tissue. Although these studies have elucidated several important aspects of this process, the structure of the organic matrix and the microenvironment where the crystal nucleates and grows are very difficult to infer from observations of the mature nacre. Here, we use environmental- and cryo-scanning electron microscopy to investigate the organic matrix structure at the onset of mineralization in the nacre of two mollusk species: the bivalves Atrina rigida and Pinctada margaritifera. These two techniques allow the visualization of hydrated biological materials coupled with the preservation of the organic matrix close to physiological conditions. We identified a hydrated gel-like protein phase filling the space between two interlamellar sheets prior to mineral formation. The results are consistent with this phase being the silk-like proteins, and show that mineral formation does not occur in an aqueous solution, but in a hydrated gel-like medium. As the tablets grow, the silk-fibroin is pushed aside and becomes sandwiched between the mineral and the chitin layer

Wigner Crystalline Edges in nu < 1 Quantum Dots

We investigate the edge reconstruction phenomenon believed to occur in quantum dots in the quantum Hall regime when the filling fraction is nu < 1. Our approach involves the examination of large dots (< 40 electrons) using a partial diagonalization technique in which the occupancies of the deep interior orbitals are frozen. To interpret the results of this calculation, we evaluate the overlap between the diagonalized ground state and a set of trial wavefunctions which we call projected necklace (PN) states. A PN state is simply the angular momentum projection of a maximum density droplet surrounded by a ring of localized electrons. Our calculations reveal that PN states have up to 99% overlap with the diagonalized ground states, and are lower in energy than the states identified in Chamon and Wen's study of the edge reconstruction.Comment: 8 pages, 8 figures, to be published in Phys. Rev.

A177: Program Evaluation of the ACR/CARRA Inter‐Institutional Mentoring Program (AMIGO) in Pediatric Rheumatology

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106776/1/art38603.pd

Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient

Autoimmune encephalitis (AE) is an important and treatable cause of acute encephalitis. Diagnosis of AE in a developing child is challenging because of overlap in clinical presentations with other diseases and complexity of normal behavior changes. Existing diagnostic criteria for adult AE require modification to be applied to children, who differ from adults in their clinical presentations, paraclinical findings, autoantibody profiles, treatment response, and long-term outcomes.A subcommittee of the Autoimmune Encephalitis International Working Group collaborated through conference calls and email correspondence to consider the pediatric-specific approach to AE. The subcommittee reviewed the literature of relevant AE studies and sought additional input from other expert clinicians and researchers.Existing consensus criteria for adult AE were refined for use in children. Provisional pediatric AE classification criteria and an algorithm to facilitate early diagnosis are proposed. There is also discussion about how to distinguish pediatric AE from conditions within the differential diagnosis.Diagnosing AE is based on the combination of a clinical history consistent with pediatric AE and supportive diagnostic testing, which includes but is not dependent on antibody testing. The proposed criteria and algorithm require validation in prospective pediatric cohorts.Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology

Total loss of MHC class I is an independent indicator of good prognosis in breast cancer

Tumours can be recognised by CTL and NK cells. CTL recognition depends on expression of MHC Class I loaded with peptides from tumour antigens. In contrast, loss of MHC Class I results in NK activation. In our study a large set of samples from patients with primary operable invasive breast cancer was evaluated for the expression of MHC Class I heavy and light by immunohistochemical staining of 439 breast carcinomas in a tissue microarray. Forty-seven percent (206 of 439) of breast carcinomas were considered negative for HLA Class I heavy chain (HC10), whereas lack of anti-β2m-antibody staining was observed in 39% (167 of 424) of tumours, with only 3% of the β2m-negative tumours expressing detectable HLA Class I heavy chain. Correlation with patient outcome showed direct relationship between patient survival and HLA-negative phenotype (log rank = 0.004). A positive relationship was found between the intensity of expression of MHC Class I light and heavy chains expression and histological grade of invasive tumour (p < 0.001) and Nottingham Prognostic Index (p < 0.001). To investigate whether HLA Class I heavy and light chains expression had independent prognostic significance, Cox multivariate regression analysis, including the parameters of tumour size, lymph node stage, grade and intensity of HC10 and anti-β2m staining, was carried out. In our analysis, lymph node stage (p < 0.001), tumour grade (p = 0.005) and intensity of MHC Class I light and heavy chains expression were shown to be independent prognostic factors predictive of overall survival (p-values HC10 = 0.047 and β2m = 0.018)

The accuracy of coronary CT angiography in patients with coronary calcium score above 1000 Agatston Units:Comparison with quantitative coronary angiography: Coronary CT Angiography in High Coronary Calcium

BACKGROUND: High amounts of coronary artery calcium (CAC) pose challenges in interpretation of coronary CT angiography (CCTA). The accuracy of stenosis assessment by CCTA in patients with very extensive CAC is uncertain. METHODS: Retrospective study was performed including patients who underwent clinically directed CCTA with CAC score >1000 and invasive coronary angiography within 90 days. Segmental stenosis on CCTA was graded by visual inspection with two-observer consensus using categories of 0%, 1–24%, 25–49%, 50–69%, 70–99%, 100% stenosis, or uninterpretable. Blinded quantitative coronary angiography (QCA) was performed on all segments with stenosis ≥25% by CCTA. The primary outcome was vessel-based agreement between CCTA and QCA, using significant stenosis defined by diameter stenosis ≥ 70%. Secondary analyses on a per-patient basis and inclusive of uninterpretable segments were performed. RESULTS: 726 segments with stenosis ≥25% in 346 vessels within 119 patients were analyzed. Median coronary calcium score was 1616 (1221–2118). CCTA identification of QCA-based stenosis resulted in a per-vessel sensitivity of 79%, specificity of 75%, positive predictive value (PPV) of 45%, negative predictive value (NPV) of 93%, and accuracy 76% (68 false positive and 15 false negative). Per-patient analysis had sensitivity 94%, specificity 55%, PPV 63%, NPV 92%, and accuracy 72% (30 false-positive and 3 false-negative). Inclusion of uninterpretable segments had variable effect on sensitivity and specificity, depending on whether they are considered as significant or non-significant stenosis. CONCLUSIONS: In patients with very extensive CAC (>1000 Agatston units), CCTA retained a negative predictive value > 90% to identify lack of significant stenosis on a per-vessel and per-patient level, but frequently overestimated stenosis

Intraocular pressure and aqueous humor flow during a euglycemic-hyperinsulinemic clamp in patients with type 1 diabetes and microvascular complications

<p>Abstract</p> <p>Background</p> <p>Microvascular complications, including retinopathy and nephropathy are seen with type 1 diabetes. It is unknown whether functional changes in aqueous humor flow or intraocular pressure (IOP) develop in parallel with these complications. This study was designed to test the hypothesis that clinical markers of microvascular complications coexist with the alteration in aqueous humor flow and IOP.</p> <p>Methods</p> <p>Ten patients with type 1 diabetes and ten healthy age- and weight-matched controls were studied. Aqueous flow was measured by fluorophotometry during a hyperinsulinemic-euglycemic clamp (insulin 2 mU/kg/min). Intraocular pressure was measured by tonometry at -10, 90 and 240 minutes from the start of the clamp, and outflow facility was measured by tonography at 240 minutes.</p> <p>Results</p> <p>During conditions of identical glucose and insulin concentrations, mean aqueous flow was lower by 0.58 μl/min in the diabetes group compared to controls (2.58 ± 0.65 versus 3.16 ± 0.66 μl/min, respectively, mean ± SD, p = 0.07) but statistical significance was not reached. Before the clamp, IOP was higher in the diabetes group (22.6 ± 3.0 mm Hg) than in the control group (19.3 ± 1.8 mm Hg, p = 0.01) but at 90 minutes into the clamp, and for the remainder of the study, IOP was reduced in the diabetes group to the level of the control group. Ocular pulse amplitude and outflow facility were not different between groups. Systolic blood pressure was significantly higher in the diabetes group, but diastolic and mean arterial pressures were not different.</p> <p>Conclusions</p> <p>We conclude that compared to healthy participants, patients with type 1 diabetes having microalbuminuria and retinopathy have higher IOPs that are normalized by hyperinsulinemia. During the clamp, a reduction in aqueous flow was not statistically significant.</p