Inflammatory Regulation of CNS Barriers After Traumatic Brain Injury: A Tale Directed by Interleukin-1

Several barriers separate the central nervous system (CNS) from the rest of the body. These barriers are essential for regulating the movement of fluid, ions, molecules, and immune cells into and out of the brain parenchyma. Each CNS barrier is unique and highly dynamic. Endothelial cells, epithelial cells, pericytes, astrocytes, and other cellular constituents each have intricate functions that are essential to sustain the brain’s health. Along with damaging neurons, a traumatic brain injury (TBI) also directly insults the CNS barrier-forming cells. Disruption to the barriers first occurs by physical damage to the cells, called the primary injury. Subsequently, during the secondary injury cascade, a further array of molecular and biochemical changes occurs at the barriers. These changes are focused on rebuilding and remodeling, as well as movement of immune cells and waste into and out of the brain. Secondary injury cascades further damage the CNS barriers. Inflammation is central to healthy remodeling of CNS barriers. However, inflammation, as a secondary pathology, also plays a role in the chronic disruption of the barriers’ functions after TBI. The goal of this paper is to review the different barriers of the brain, including (1) the blood-brain barrier, (2) the blood-cerebrospinal fluid barrier, (3) the meningeal barrier, (4) the blood-retina barrier, and (5) the brain-lesion border. We then detail the changes at these barriers due to both primary and secondary injury following TBI and indicate areas open for future research and discoveries. Finally, we describe the unique function of the pro-inflammatory cytokine interleukin-1 as a central actor in the inflammatory regulation of CNS barrier function and dysfunction after a TBI

ОСОБИСТІСНО-ОРІЄНТОВАНИЙ ПІДХІД ЯК ОДИН ІЗ ОСНОВОПОЛОЖНИХ ДИДАКТИЧНИХ ПРИНЦИПІВ ВИКЛАДАННЯ ДИСЦИПЛІНИ “ХІРУРГІЯ” НА КАФЕДРІ ХІРУРГІЇ № 1 З УРОЛОГІЄЮ ТА МАЛОІНВАЗИВНОЮ ХІРУРГІЄЮ ІМЕНІ ПРОФ. Л. Я. КОВАЛЬЧУКА ТЕРНОПІЛЬСЬКОГО ДЕРЖАВНОГО МЕДИЧНОГО УНІВЕРСИТЕТУ ІМЕНІ І. Я. ГОРБАЧЕВСЬКОГО

The aim of the work – to share the experience of organizing the educational process at the L. Ya. Kovalchuk Department of Surgery No. 1 with Urology and Minimally Invasive Surgery,  I. Horbachevsky Ternopil State Medical University  on the basis of a person-oriented approach.The main body. Personality-oriented approach in pedagogy is designed to provide the widest possible opportunities for the comprehensive development of the student’s personality. Based on the foregoing, modern higher education envisages a fundamental practical training and a comprehensive development of a holistic, socially adapted personality. Didactic principles of the organization of the educational process in our institution determine the internal university normative documents. Department of Surgery No. 1 with Urology and Minimally Invasive Surgery named after prof. L. Ya. Kovalchuk prepared working programs for the fourth, fifth and sixth courses of the medical university, which envisages the structuring of the subject into practical and theoretical parts, the distribution of hours for practical classes and self-development. Organization of study using the “One Day” method allows to allocate enough time for communication of the teacher with each student of the academic group, because 6 hours are allocated for conducting classes with one group. Practical work carried out “near the bed of the patient”, the possibility of communication with the patient, the opportunity to take part in all stages of hospitalization of the patient and in all stages of his treatment, as well as visiting the library, the computer class of the department during the hour of independent work of students, the seminar discussion and control of knowledge, provides the opportunity to fully consolidate the material to the student and assess his level of knowledge by the teacher.Conclusion. Didactic forms of teaching the discipline of Surgery at the L.Ya. Kovalchuk Department of Surgery No. 1 with Urology and Minimally Invasive Surgery, I. Horbachevsky Ternopil State Medical University respond to the principle of a person – oriented approach in higher medical education and not only  ensure the formation of professional competencies provided by the current educational standards, but also contribute to the comprehensive development of the personality of the future doctor.Мета роботи – поділитися досвідом організації навчального процесу на кафедрі хірургії № 1 з урологією та малоінвазивною хірургією імені проф. Л. Я. Ковальчука Тернопільського державного медичного університету імені І. Я. Горбачевського на засадах особистісно-орієнтованого підходу.Основна частина. Особистісно-орієнтований підхід у педагогіці покликаний забезпечити максимально широкі можливості для всебічного розвитку особистості студента. Виходячи із вищенаведеного, сучасна вища освіта передбачає фундаментальну практично-професійну підготовку та всебічний розвиток цілісної, соціально адаптованої особистості.Дидактичні засади організації навчального процесу в нашому закладі визначають внутрішні університетські нормативні документи. Кафедрою хірургії № 1 з урологією та малоінвазивною хірургією імені проф. Л. Я. Ковальчука складено робочі програми на четвертий, п’ятий та шостий курси медичного університету, якими передбачено структурування предмета на практичну та теоретичну частини, розподіл годин на практичні заняття та самоопрацювання. Організація навчання за методикою “Єдиного дня” дозволяє приділити достатньо часу спілкуванню викладача з кожним студентом академічної групи, адже 6 годин виділені на проведення заняття з однією групою. Практична робота, проведена “біля ліжка хворого”, можливість с пілкування з пацієнтом, можливість брати участь у всіх етапах госпіталізації хворого та у всіх етапах його лікування, а також відвідування бібліотеки, комп’ютерного класу кафедри під час години самостійної роботи студентів, семінарське обговорення та контроль знань дають можливість повноцінно закріпити матеріал студенту й оцінити рівень його знань викладачем.Висновок. Дидактичні форми організації викладання дисципліни “Хірургія”  кафедрою хірургії № 1 з урологією та малоінвазивною хірургією імені проф. Л. Я. Ковальчука Тернопільського державного медичного університету імені І. Я. Горбачевського відповідають принципу особистісно-орієнтованого підходу у вищій медичній освіті та не тільки забезпечують формування професійних компетенцій, передбачених чинними галузевими стандартами, але й сприяють всебічному розвитку особистості майбутнього лікаря

Electric-field-induced nematic-cholesteric transition and 3-D director structures in homeotropic cells

We study the phase diagram of director structures in cholesteric liquid crystals of negative dielectric anisotropy in homeotropic cells of thickness d which is smaller than the cholesteric pitch p. The basic control parameters are the frustration ratio d/p and the applied voltage U. Fluorescence Confocal Polarising Microscopy allows us to directly and unambiguously determine the 3-D director structures. The results are of importance for potential applications of the cholesteric structures, such as switchable gratings and eyewear with tunable transparency based.Comment: Will be published in Physical Review

Impact of pyridine-2-carboxaldehyde-derived aroylhydrazones on the copper-catalyzed oxidation of the M112A PrP_103-112 mutant fragment.

Misfolded prion protein (PrPSc) is known for its role in fatal neurodegenerative conditions, such as Creutzfeldt-Jakob disease. PrP fragments and their mutants represent important tools in the investigation of the neurotoxic mechanisms and in the evaluation of new compounds that can interfere with the processes involved in neuronal death. Metal-catalyzed oxidation of PrP has been implicated as a trigger for the conformational changes in protein structure, which, in turn, lead to misfolding. Targeting redox-active biometals copper and iron is relevant in the context of protection against the oxidation of biomolecules and the generation of oxidative stress, observed in several conditions and considered an event that might promote sporadic prion diseases as well as other neurodegenerative disorders. In this context, ortho-pyridine aroylhydrazones are of interest, as they can act as moderate tridentate ligands towards divalent metal ions such as copper(II). In the present work, we explore the potentiality of this chemical class as peptide protecting agents against the deleterious metal-catalyzed oxidation in the M112A mutant fragment of human PrP, which mimics relevant structural features that may play an important role in the neurotoxicity observed in prion pathologies. The compounds inhere studied, especially HPCFur, showed an improved stability in aqueous solution compared to our patented lead hydrazone INHHQ, displaying a very interesting protective effect toward the oxidation of methionine and histidine, processes that are related to both physiological and pathological aging

Influence of polymer excluded volume on the phase behavior of colloid-polymer mixtures

We determine the depletion-induced phase-behavior of hard sphere colloids and interacting polymers by large-scale Monte Carlo simulations using very accurate coarse-graining techniques. A comparison with standard Asakura-Oosawa model theories and simulations shows that including excluded volume interactions between polymers leads to qualitative differences in the phase diagrams. These effects become increasingly important for larger relative polymer size. Our simulations results agree quantitatively with recent experiments.Comment: 5 pages, 4 figures submitted to Physical Review Letter

Overturning established chemoselectivities : selective reduction of arenes over malonates and cyanoacetates by photoactivated organic electron donors

The prevalence of metal-based reducing reagents, including metals, metal complexes, and metal salts, has produced an empirical order of reactivity that governs our approach to chemical synthesis. However, this reactivity may be influenced by stabilization of transition states, intermediates, and products through substrate-metal bonding. This article reports that in the absence of such stabilizing interactions, established chemoselectivities can be overthrown. Thus, photoactivation of the recently developed neutral organic superelectron donor 5 selectively reduces alkyl-substituted benzene rings in the presence of activated esters and nitriles, in direct contrast to metal-based reductions, opening a new perspective on reactivity. The altered outcomes arising from the organic electron donors are attributed to selective interactions between the neutral organic donors and the arene rings of the substrates

Lipid-soluble Vitamins A, D, and E in HIV-Infected Pregnant women in Tanzania.

There is limited published research examining lipid-soluble vitamins in human immunodeficiency virus (HIV)-infected pregnant women, particularly in resource-limited settings. This is an observational analysis of 1078 HIV-infected pregnant women enrolled in a trial of vitamin supplementation in Tanzania. Baseline data on sociodemographic and anthropometric characteristics, clinical signs and symptoms, and laboratory parameters were used to identify correlates of low plasma vitamin A (<0.7 micromol/l), vitamin D (<80 nmol/l) and vitamin E (<9.7 micromol/l) status. Binomial regression was used to estimate risk ratios and 95% confidence intervals. Approximately 35, 39 and 51% of the women had low levels of vitamins A, D and E, respectively. Severe anemia (hemoglobin <85 g/l; P<0.01), plasma vitamin E (P=0.02), selenium (P=0.01) and vitamin D (P=0.02) concentrations were significant correlates of low vitamin A status in multivariate models. Erythrocyte Sedimentation Rate (ESR) was independently related to low vitamin A status in a nonlinear manner (P=0.01). The correlates of low vitamin D status were CD8 cell count (P=0.01), high ESR (ESR >81 mm/h; P<0.01), gestational age at enrollment (nonlinear; P=0.03) and plasma vitamins A (P=0.02) and E (P=0.01). For low vitamin E status, the correlates were money spent on food per household per day (P<0.01), plasma vitamin A concentration (nonlinear; P<0.01) and a gestational age <16 weeks at enrollment (P<0.01). Low concentrations of lipid-soluble vitamins are widely prevalent among HIV-infected women in Tanzania and are correlated with other nutritional insufficiencies. Identifying HIV-infected persons at greater risk of poor nutritional status and infections may help inform design and implementation of appropriate interventions