Mechanical Analysis of Atherosclerotic Plaques Based on Optical Coherence Tomography

Finite element analysis is a powerful tool for investigating the biomechanics of atherosclerosis and has thereby provided an improved understanding of acute myocardial infarction. Structural analysis of arterial walls is traditionally performed using geometry contours derived from histology. In this paper we demonstrate the first use of a new imaging technique, optical coherence tomography (OCT), as a basis for finite element analysis. There are two primary benefits of OCT relative to histology: 1) imaging is performed without excessive tissue handling, providing a more realistic geometry than histology and avoiding structural artifacts common to histologic processing, and 2) OCT imaging can be performed in vivo, making it possible to study disease progression and the effect of therapeutic treatments in animal models and living patients. Patterns of mechanical stress and strain distributions computed from finite element analysis based on OCT were compared with those from modeling based on "gold standard" histology. Our results indicate that vascular structure and composition determined by OCT provides an adequate basis for investigating the biomechanical factors relevant to atherosclerosis and acute myocardial infarction.     

Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound

OBJECTIVES: The aim of this study was to evaluate the feasibility and the ability of intravascular optical coherence tomography (OCT) to visualize the components of coronary plaques in living patients. BACKGROUND: Disruption of a vulnerable coronary plaque with subsequent thrombosis is currently recognized as the primary mechanism for acute myocardial infarction. Although such plaques are considered to have a thin fibrous cap overlying a lipid pool, imaging modalities in current clinical practice do not have sufficient resolution to identify thin (< 65 microm) fibrous caps. Optical coherence tomography is a new imaging modality capable of obtaining cross-sectional images of coronary vessels at a resolution of approximately 10 microm. METHODS: The OCT images and corresponding histology of 42 coronary plaques were compared to establish OCT criteria for different types of plaques. Atherosclerotic lesions with mild to moderate stenosis were identified on angiograms in 10 patients undergoing cardiac catheterization. Optical coherence tomography and intravascular ultrasound (IVUS) images of these sites were obtained in all patients without complication. RESULTS: Comparison between OCT and histology demonstrated that lipid-rich plaques and fibrous plaques have distinct OCT characteristics. A total of 17 IVUS and OCT image pairs obtained from patients were compared. Axial resolution measured 13 +/- 3 microm with OCT and 98 +/- 19 microm with IVUS. All fibrous plaques, macrocalcifications and echolucent regions identified by IVUS were visualized in corresponding OCT images. Intimal hyperplasia and echolucent regions, which may correspond to lipid pools, were identified more frequently by OCT than by IVUS. CONCLUSIONS: Intracoronary OCT appears to be feasible and safe. Optical coherence tomography identified most architectural features detected by IVUS and may provide additional detailed structural information.     

An update on the treatment of pediatric-onset Langerhans cell histiocytosis through pharmacotherapy

Introduction: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasia driven by activation mutations alongside the MAPK pathway. Its broad spectrum of clinical manifestations and diverse course and clinical outcome, make interpretation of trial data difficult. Use of different stratification systems further complicates comparison among trials.

Areas covered: This review summarizes the published data derived from prospective clinical trials from Phase II onwards. PubMed was searched using combinations of the keywords ‘Langerhans cell histiocytosis’, ‘histiocytosis X’, ‘pediatric’, ‘children’, ‘treatment’, and ‘therapy’. Only full-length papers published in English and German were included in the review.

Expert opinion: Mortality in multisystem LCH is restricted to patients with involvement of risk organs (hematopoiesis, liver and spleen) at diagnosis, and is particularly high (up to 60–70%) if systemic therapy fails to control the disease. For the rest of the cohort, mortality is almost negligible, and the main challenges are disease relapses and related permanent consequences (encountered in up to 50% of the survivors). While systemic therapy has clearly improved survival of patients with most severe disease form, its role in providing sustained disease control and preventing permanent consequences in patients with ‘low risk’ disease is less clear.     

Quantum cluster algebras and quantum nilpotent algebras

A major direction in the theory of cluster algebras is to construct (quantum) cluster algebra structures on the (quantized) coordinate rings of various families of varieties arising in Lie theory. We prove that all algebras in a very large axiomatically defined class of noncommutative algebras possess canonical quantum cluster algebra structures. Furthermore, they coincide with the corresponding upper quantum cluster algebras. We also establish analogs of these results for a large class of Poisson nilpotent algebras. Many important families of coordinate rings are subsumed in the class we are covering, which leads to a broad range of applications of the general results to the above-mentioned types of problems. As a consequence, we prove the Berenstein–Zelevinsky conjecture [Berenstein A, Zelevinsky A (2005) Adv Math 195:405–455] for the quantized coordinate rings of double Bruhat cells and construct quantum cluster algebra structures on all quantum unipotent groups, extending the theorem of Geiß et al. [Geiß C, et al. (2013) Selecta Math 19:337–397] for the case of symmetric Kac–Moody groups. Moreover, we prove that the upper cluster algebras of Berenstein et al. [Berenstein A, et al. (2005) Duke Math J 126:1–52] associated with double Bruhat cells coincide with the corresponding cluster algebras.The theory of cluster algebras provides a unified framework for treating a number of problems in diverse areas of mathematics such as combinatorics, representation theory, topology, mathematical physics, algebraic and Poisson geometry, and dynamical systems (1–7). The construction of cluster algebras was invented by Fomin and Zelevinsky (1), who also obtained a number of fundamental results on them. This construction builds algebras in a novel way by producing infinite generating sets via a process of mutation rather than the classical approach using generators and relations.The main algebraic approach to cluster algebras relies on representations of finite dimensional algebras and derived categories (5, 8). In this paper, we describe a different algebraic approach based on noncommutative ring theory.An important range of problems in the theory of cluster algebras is to prove that the coordinate rings of certain algebraic varieties coming from Lie theory admit cluster algebra structures. The idea is that once this is done, one can use cluster algebras to study canonical bases in such coordinate rings. Analogous problems deal with the corresponding quantizations. The approach via representation theory to this type of problem needs combinatorial data for quivers as a starting point. Such might not be available a priori. This approach also differs from one family of varieties to another, which means that one needs to design an appropriate categorification process in each case.We prove that all algebras in a very general, axiomatically defined class of quantum nilpotent algebras are quantum cluster algebras. The proof is based on constructing quantum clusters by considering sequences of prime elements in chains of subalgebras that are noncommutative unique factorization domains (UFDs). These clusters are canonical relative to the mentioned chains of subalgebras, which are determined by the presentation of the quantum nilpotent algebra. The construction does not rely on any initial combinatorics of the algebras. On the contrary, the construction itself produces intricate combinatorial data for prime elements in chains of subalgebras. When this is applied to special cases, we recover the Weyl group combinatorics that played a key role in categorification earlier (7, 9, 10). Because of this, we expect that our construction will be helpful in building a unified categorification of quantum nilpotent algebras. Finally, we also prove similar results for (commutative) cluster algebras using Poisson prime elements.The results of the paper have many applications because a number of important families of algebras arise as special cases in our axiomatics. Berenstein et al. (10) proved that the coordinate rings of all double Bruhat cells in every complex simple Lie group are upper cluster algebras. It was an important problem to decide whether the latter coincide with the corresponding cluster algebras. We resolve this problem positively. On the quantum side, we prove the Berenstein–Zelevinsky conjecture (11) on cluster algebra structures for all quantum double Bruhat cells. Finally, we establish that the quantum Schubert cell algebras for all complex simple Lie groups have quantum cluster algebra structures. Previously this was known for symmetric Kac–Moody groups due to Geiß et al. (12).     

Therapeutic potential of phenylethanoid glycosides: A systematic review

Phenylethanoid glycosides (PhGs) are generally water-soluble phenolic compounds that occur in many medicinal plants. Until June 2020, more than 572 PhGs have been isolated and identified. PhGs possess antibacterial, anticancer, antidiabetic, anti-inflammatory, antiobesity, antioxidant, antiviral, and neuroprotective properties. Despite these promising benefits, PhGs have failed to fulfill their therapeutic applications due to their poor bioavailability. The attempts to understand their metabolic pathways to improve their bioavailability are investigated. In this review article, we will first summarize the number of PhGs compounds which is not accurate in the literature. The latest information on the biological activities, structure–activity relationships, mechanisms, and especially the clinical applications of PhGs will be reviewed. The bioavailability of PhGs will be summarized and factors leading to the low bioavailability will be analyzed. Recent advances in methods such as bioenhancers and nanotechnology to improve the bioavailability of PhGs are also summarized. The existing scientific gaps of PhGs in knowledge are also discussed, highlighting research directions in the future.     

Behaviour of Impurities during Electron Beam Melting of Copper Technogenic Material

The current study presents the electron beam melting (EBM) efficiency of copper technogenic material with high impurity content (Se, Te, Pb, Bi, Sn, As, Sb, Zn, Ni, Ag, etc.) by means of thermodynamic analysis and experimental tests. On the basis of the calculated values of Gibbs free energy and the physical state of the impurity (liquid and gaseous), a thermodynamic assessment of the possible chemical interactions occurring in the Cu-Cu₂O-Me_x system in vacuum in the temperature range 1460–1800 K was made. The impact of the kinetic parameters (temperature and refining time) on the behaviour and the degree of removal of impurities was evaluated. Chemical and metallographic analysis of the obtained ingots is also discussed.     

Transcobalamin II deficiency at birth

Transcobalamin II deficiency (# MIM 275350) is a rare, recessively inherited disorder of cobalamin transport that leads to intracellular cobalamin depletion with secondary impairment of methionine synthetase and methyl-malonyl CoA mutase activities. Affected individuals may suffer from long-term neurological sequelae if therapy with intramuscular hydroxocobalamin is not initiated promptly. We report two sisters with complete absence of transcobalamin due to homozygosity for a novel mutation (c.insC110) in the TCN2 gene that leads to a premature stop codon and non-functional protein. The older sister, now 4.5 years old, presented at 6 weeks of age with pancytopenia, protein losing enteropathy and a rapidly declining clinical course. Prompt therapy with 1 mg hydroxocobalamin/day led to full recovery within days. Her now 1.5 year old sister was diagnosed shortly after birth and was started on hydroxocobalamin prior to onset of clinical symptoms. Interestingly, urinary methylmalonic acid excretion was increased significantly during the first days of life suggesting that functional cobalamin deficiency is present also during fetal life, although not giving rise to clinical symptoms until well after birth.