The Relativistic Electrodynamics Least Action Principles Revisited: New Charged Point Particle and Hadronic String Models Analysis

The classical relativistic least action principle is revisited from the vacuum field theory approach. New physically motivated versions of relativistic Lorentz type forces are derived, a new relativistic hadronic string model is proposed and analyzed in detail.Comment: n/

The Vacuum Structure, Special Relativity and Quantum Mechanics Revisited: a Field Theory No-Geometry Approach within the Lagrangian and Hamiltonian Formalisms. Part 2

The main fundamental principles characterizing the vacuum field structure are formulated and the modeling of the related vacuum medium and charged point particle dynamics by means of devised field theoretic tools are analyzed. The work is devoted to studying the vacuum structure, special relativity, electrodynamics of interacting charged point particles and quantum mechanics, and is a continuation of \cite{BPT,BRT1}. Based on the vacuum field theory no-geometry approach, the Lagrangian and Hamiltonian reformulation of some alternative classical electrodynamics models is devised. The Dirac type quantization procedure, based on the canonical Hamiltonian formulation, is developed for some alternative electrodynamics models. Within an approach developed a possibility of the combined description both of electrodynamics and gravity is analyzed.Comment: 11 page

Heart Injury in Juvenile Systemic Sclerodermy (Clinical Case)

Juvenile systemic sclerosis (JSS) has many clinical manifestations that differ from adults. Early diagnosis is problematic. The course of the disease and the severity of the prognosis depend on the involvement of internal organs in the process, first of all, the heart, lungs, kidneys. Cardiac pathology is a frequent and prognostically unfavorable target of the scleroderma process in adults, but it is rarely diagnosed in children. The aim of the work was to study the features of the clinical manifestations of systemic sclerosis in a child with severe heart disease. A polymorphism of the clinical symptoms of severe heart damage with the development of dilated cardiomyopathy in a one-year-old child with systemic sclerosis is presented. The features of the case are the early debut of systemic sclerosis in a child with a burdened hereditary history of autoimmune pathology (psoriasis in the father and grandmother), rapid progression of the autoimmune process, severe heart damage by the type of non-compact (dilated) cardiomyopathy, positive clinical dynamics when using pathogenetic therapy. Early detection of cardiovascular lesions using modern diagnostic methods, timely implementation of adequate therapy in a multidisciplinary team and regular cardiovascular screening can improve the prognosis, quality of life and reduce mortality

Blockade of a Laminin-411–Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk

There is an unmet need for the treatment of glioblastoma multiforme (GBM). The extracellular matrix, including laminins, in the tumor microenvironment is important for tumor invasion and progression. In a panel of 226 patient brain glioma samples, we found a clinical correlation between the expression of tumor vascular laminin-411 (alpha 4 beta 1 gamma 1) with higher tumor grade and with expression of cancer stem cell (CSC) markers, including Notch pathway members, CD133, Nestin, and c-Myc. Laminin-411 overexpression also correlated with higher recurrence rate and shorter survival of GBM patients. We also showed that depletion of laminin-411 alpha 4 and beta 1 chains with CRISPR/Cas9 in human GBM cells led to reduced growth of resultant intracranial tumors in mice and significantly increased survival of host animals compared with mice with untreated cells. Inhibition of laminin-411 sup-pressed Notch pathway in normal and malignant human-brain cell types. A nanobioconjugate potentially suitable for clinical use and capable of crossing blood-brain barrier was designed to block laminin-411 expression. Nanobioconjugate treatment of mice carrying intracranial GBMsignificantly increased animal survival and inhibited multiple CSC markers, including the Notch axis. This study describes an efficient strategy for GBMtreatment via targeting a critical component of the tumor microenvironment largely independent of heterogeneous genetic mutations in glioblastoma. Significance: Laminin-411 expression in the glioma microenvironment correlates with Notch and other cancer stem cell markers and can be targeted by a novel, clinically translatable nanobioconjugate to inhibit glioma growth