Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities

The pathophysiology of multiple sclerosis (MS) involves several components: redox, inflammatory/autoimmune, vascular, and neurodegenerative. All of them are supported by the intertwined lines of evidence, and none of them should be written off. However, the exact mechanisms of MS initiation, its development, and progression are still elusive, despite the impressive pace by which the data on MS are accumulating. In this review, we will try to integrate the current facts and concepts, focusing on the role of redox changes and various reactive species in MS. Knowing the schedule of initial changes in pathogenic factors and the key turning points, as well as understanding the redox processes involved in MS pathogenesis is the way to enable MS prevention, early treatment, and the development of therapies that target specific pathophysiological components of the heterogeneous mechanisms of MS, which could alleviate the symptoms and hopefully stop MS. Pertinent to this, we will outline (i) redox processes involved in MS initiation; (ii) the role of reactive species in inflammation; (iii) prooxidative changes responsible for neurodegeneration; and (iv) the potential of antioxidative therapy. Antioxid. Redox Signal. 19, 2286-2334

Juveniles as victims of criminal acts committed under the misuse of computer network

The fact is that technological development has improved many aspects of life, but at the same time, according to the principle of a double-edged sword, it created justifiable fear in view of the numerous negative consequences of its misuse. A special segment of technological development where such misuses are increasingly present are computer networks. Such fear is further expressed when it comes to juveniles, who, due to the characteristics of this development period, represent easy targets, which often leads to serious and long-term consequences. Although this category of people, as a rule, works well with such innovations, their inexperience can easily put them in danger. For the above reasons, this problem should be approached from a theoretical point of view. It seems that questions that have been discussed in this paper deserve special attention: the impact of internet dependency on victimization; typology of juvenile victims; characteristics of victims of internet pedophilia. The use of meta-analysis has resulted in the synthesis of the results of existing research and attitudes, which served as a basis for a critical review and an attempt to give a modest contribution to solving these issues

Investigation of large-diameter flange joint with soft-gasket

U središtu je interesa ovog rada ponašanje spojeva prirubnice i mekane gumene brtve koja je tipična vrsta brtve za isparivače. Montirana konstrukcija ispitala se prema normi EN 13445-3, a naprezanja su se mjerila tenzometrima. Numerička analiza u programskom paketu ABAQUS obuhvaćala je nekoliko modela s različitim detaljima. Ti su modeli bili podešeni u skladu sa zabilježenim podacima iz ispitivanja. U radu su prikazane i dokumentirane preporuke koje se tiču složenosti modela koji je potreban kako bi se postigla zadovoljavajuća razina predviđanja nelinearnog ponašanja spojeva prirubnica.This study focuses on behaviour of the flanged joint with a soft rubber gasket, which is a common type of gasket for evaporator structures. The assembled structure is tested according to EN 13445-3, and strain values are measured using strain gauges. The numerical analysis in ABAQUS comprises several models with different levels of detail. These models are calibrated according to test data. Recommendations regarding the model complexity that is required to obtain satisfactory prediction of non-linear behaviour of flange joints are presented and documented

Maligna kataralna groznica (Coryza gangraenosa bovum)

Malignant catarrhal fever is a disease of cattle and other ruminants, which most often has a lethal outcome. The disease occurs sporadically and is very difficult to control. At a private mini cattle farm, the occurrence of malignant catarrhal fever was suspected on the grounds of anaemnestic data and results of clinical examinations. The owner said that, in addition to cattle, he also breeds sheep in a separate facility, but said these animals had not been in contact with the diseased cow. In the course of the disease, the characteristic symptoms developed so that the clinical diagnosis set earlier was subsequently confirmed. In addition to constantly elevated body temperature, changes in the eyes were observed very soon (congested blood vessels and capillaries of the white sclera with keratitis on both sides). In addition to photofobia and a copious discharge from the nasal cavities, the discharge was at first seromucous and later became mucopurrulent. In the later course of the disease, there was progressive loss of weight and exhaustion of the animal. Since therapy included, in addition to other medicines, also a glucocorticosteroid preparation, the animal aborted its fetus on the fifth day. A pathological-anatomical examination did not reveal any changes on the fetus. In spite of the applied therapy, the medical condition deteriorated from day to day, and the animal expired on the eighth day of the disease.Maligna kataralna groznica je oboljenje goveda i drugih preživara, koje se najčešće završava uginućem. Bolest se pojavljuje sporadično i veoma se teško kontroliše. Na privatnoj mini-farmi goveda na osnovu anamnestičkih podataka i rezultata kliničkog pregleda postavljena je sumnja na malignu kataralnu groznicu. Vlasnik je izjavio da pored goveda u posebnom objektu gaji ovce, ali kako je on naveo one nisu bile u kontaktu sa obolelom životinjom. U toku bolesti je došlo do razvoja karakterističnih simptoma tako da je prethodno postavljena klinička dijagnoza potvrđena. Pored stalno povišene telesne temperature, veoma brzo su uočene i promene na očima (kongestija krvnih sudova i kapilara beonjača sa obostranim keratitisom). Pored fotofobije i obilnog suženja, iz nosnih otvora slivao se u početku seromukozan, a kasnije i mukopurulentan iscedak. U kasnijem razvoju bolesti došlo je do progresivnog mršavljenja i iscrpljenosti životinje. Pošto je u terapiji, pored drugih lekova, korišćen preparat glukokortikosteroida, životinja je petog dana pobacila plod. Patološkoanatomskim pregledom nisu uočene promene na plodu. Uprkos primenjenoj terapiji, zdravstveno stanje životinje se pogoršavalo iz dana u dan i osmog dana bolovanja ona je uginula

SMART, ERGONOMIC AND SUSTAINABLE MINING MACHINERY WORKPLACES: AN OVERVIEW OF THE SMARTMINER PROJECT

Despite being the oldest, the mining industry continues to be a major source of pollution, with more people killed or injured than in all other industries. Additionally, social tension related to this sector is widespread around the world, since mining businesses continue to have a significant negative influence on land, water, air, biota, and people through direct and indirect mechanisms. The mining machinery workplaces, which are in the focus of this study have the largest environmental footprint. The dominance of technology-centered design in present research streams is most likely the explanation for the lack of advancement in the mining industry. The SmartMiner project creates shift from technology-centered design and its concept creates solutions for improving the standard of environmental quality in complex systems and suggests a paradigm change to a Human and Data-Centric Engineering. By aligning advanced operator I4.0&5.0 and society S5.0 standards, the SmartMiner project develops solutions for raising the level of environmental quality in complex interactions between physical, behavioural, and organizational processes field. Proposed paradigm can be easily transferred to other industries. The safety of mining machinery operators in their immediate surroundings and their regular alignment with value chain stakeholders are the first steps in our original idea approval process. Research moves to the operator macro-environment, which is determined by organizational contextual factors, and is encompassed by the development of intelligent, ergonomic, non-invasive, and dependable operator aid systems for regulating physical environment job stressors - noise, human vibration, lighting, temperature, air quality, workplace layout issues, etc., with high potential to solve environmental and human health issues and to influence overall performance

Molecular genetics of autochthonous lactic acid bacteria

Autohtoni sojevi bakterija mlečne kiseline (BMK) su izolovane iz fermentisanih mlečnih proizvoda rađenih u domaćoj radinosti. Fermentisani mlečni proizvodi su sakupljani sa specifičnih ekoloških lokaliteta kao što su visoke planine (iznad 1200 m nadmorske visine), planinske visoravni, rečne doline, ostrva, obala Jadranskog mora, itd. Analiza kolekcije prirodnih izolata BMK je pokazala da izolati proizvode proteinaze, bakteriocine i egzopolisaharide. Pokazano je, takođe, da neki izolati laktokoka i laktobacila proizvode istovremeno dva različita bakteriocina. Pored toga određeni broj izolata proizvodi i proteinaze i bakteriocine. Nađeno je da prirodni izolati sintetišu specifične proteinaze. Analiza organizacije prt gena u prirodnim izolatima BMK je pokazala da četiri laktobacila poseduju organizaciju prt gena koja se razlikuje od do sada opisanih. Izučavanje regulacije gena koji kodiraju proteinaze, bakteriocine ili egzopolisaharide može olakšati konstrukciju specifičnih starter kultura za proizvodnju autohtonih fermentisanih mlečnih proizvoda, tj. fermentisanih proizvoda sa geografskim poreklom.Autochthonous strains of lactic acid bacteria (LAB) were isolated from homemade fermented milk products. These products were collected from specific ecological localities such as high mountains (above 1200 m above sea level) mountain plateaus, river valleys, islands, Adriatic coast, etc. Analysis of LAB from the collection of natural isolates revealed that they produce proteinases, bacteriocins and exopolysaccharides. It was also shown that some isolates of lactococci and lactobacilli produce two bacteriocins simultaneously. According to their antimicrobial and biochemical properties most of the analyzed bacteriocins in natural isolates of lactococci were class 11 bacteriocins. In addition some isolates produced both proteinase and bacteriocin. Biosynthesis of specific proteinases was detected in natural isolates. Analysis of the prt gene organization among natural isolates of LAB showed that four isolates of lactobacilli exhibited prt genes organization different from those described so far. Elucidation of the regulation of the genes encoding proteinases, bacteriocins and exopolysaccharides could facilitate the construction of specific starter cultures for production of autochthonous fermented milk products, i.e. fermented products with a geographical origin

Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities

The pathophysiology of multiple sclerosis (MS) involves several components: redox, inflammatory/autoimmune, vascular, and neurodegenerative. All of them are supported by the intertwined lines of evidence, and none of them should be written off. However, the exact mechanisms of MS initiation, its development, and progression are still elusive, despite the impressive pace by which the data on MS are accumulating. In this review, we will try to integrate the current facts and concepts, focusing on the role of redox changes and various reactive species in MS. Knowing the schedule of initial changes in pathogenic factors and the key turning points, as well as understanding the redox processes involved in MS pathogenesis is the way to enable MS prevention, early treatment, and the development of therapies that target specific pathophysiological components of the heterogeneous mechanisms of MS, which could alleviate the symptoms and hopefully stop MS. Pertinent to this, we will outline (i) redox processes involved in MS initiation; (ii) the role of reactive species in inflammation; (iii) prooxidative changes responsible for neurodegeneration; and (iv) the potential of antioxidative therapy. Antioxid. Redox Signal. 19, 2286-2334.Ministry of Education and Science of the Republic of Serbia [OI173014, OI173035

Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities

The pathophysiology of multiple sclerosis (MS) involves several components: redox, inflammatory/autoimmune, vascular, and neurodegenerative. All of them are supported by the intertwined lines of evidence, and none of them should be written off. However, the exact mechanisms of MS initiation, its development, and progression are still elusive, despite the impressive pace by which the data on MS are accumulating. In this review, we will try to integrate the current facts and concepts, focusing on the role of redox changes and various reactive species in MS. Knowing the schedule of initial changes in pathogenic factors and the key turning points, as well as understanding the redox processes involved in MS pathogenesis is the way to enable MS prevention, early treatment, and the development of therapies that target specific pathophysiological components of the heterogeneous mechanisms of MS, which could alleviate the symptoms and hopefully stop MS. Pertinent to this, we will outline (i) redox processes involved in MS initiation; (ii) the role of reactive species in inflammation; (iii) prooxidative changes responsible for neurodegeneration; and (iv) the potential of antioxidative therapy. Antioxid. Redox Signal. 19, 2286-2334.Ministry of Education and Science of the Republic of Serbia [OI173014, OI173035

Uticaj neutralizacije na svojstva poroznih hidrogelova na bazi hidroksiapatita i poli(metakrilne kiseline) sintetisanih slobodno-radikalskom polimerizacijom

Goals. The goal of this study was a development of biocompatible composite hydrogels, structurally similar to native bone tissue, by incorporation of ~60 wt % of calcium hydroxyapatite (HA) into a matrix of hydrogels. Also, a possibility to control swelling kinetic and equilibrium swelling degree (SDeq) of hydrogels, by altering the degree of neutralization of the precursor (DN) was examined. Methods. Composite hydrogels, based on HA and poly(methacrylic acid) (PMAA), were synthesized by free-radical polymerization with different DN. Theoretical content of HA in synthesized composites was 60 wt %. Composites were synthesized by methods of dynamic mechanical analysis and scanning electron microscopy. SDeq and swelling kinetic were examined in distilled water and simulated body fluid. Results. Morphological observations revealed uniform distribution and strong bond of spherical HA particles within the polymer matrix. Swelling analyses demonstrated that SDeq is directly proportional to DN, while rheological examinations indicated inverse proportion between DN and storage modulus, but due to the HA particles inclusion, mechanical properties of composites were significantly better compared to monophasic PMAA hydrogels. Significance. Simple method of synthesis of composite hydrogels with high content of filler nanoparticles is presented. Incorporation of HA nanoparticles significantly improved mechanical properties of hydrogels, while at the same time was demonstrated a possibility to control swelling kinetic by influencing the DN.Ciljevi - Cilj ove studije bio je razvoj biokompatibilnih kompozitnih hidrogelova, koji su slične strukture kao prirodno koštano tkivo, inkorporacijom ∼60 mas % kalcijum-hidroksiapatita (HA) u matricu hidro-gela. Takođe, ispitan je uticaj neutralizacije prekursora polimerne mreže na kinetiku bubrenja i ravnotežni stepen bubrenja (SDeq).Metode - Kompozitni hidrogelovi, sastavljeni od HA i poli(metakrilne kiseline) (PMAA), sintetisani su slobodno-radikalskom polimerizacijom, pri različitim stepenima neutralizacije prekursora (SN). Svi sintetisani kompoziti sadrže visok maseni udeo HA (~60 mas %). Kompoziti su okarakterisani metodama skenirajuće elektronske mikroskopije (SEM) i dinamičko-mehaničke analize (DMA). SDeq i kinetika bubrenja ispitivani su u destilovanoj vodi i simuliranoj telesnoj tečnosti (SBF). Rezultati - Morfološka ispitivanja pokazala su uniformnu raspodelu i dobru povezanost sferičnih čestica apatita sa polimernom matricom. Analiza procesa bubrenja pokazala je proporcionalnu zavisnost SN i SDeq kompozita. Reološka ispitivanja ukazala su na obrnuto proporcionalnu zavisnost između SN i vrednosti modula sačuvane energije, koji su iznosili 55130 Pa u slučaju potpune neutralizacije i 77480 Pa u slučaju 0% neutralizacije. Značaj - Predstavljena je jednostavna metoda za sintezu kompozitnih hidrogelova sa visokim masenim udelom nanočestica punioca. Inkorporacijom nanočestica HA postignuto je značajno poboljšanje mehaničkih svojstava hidrogelova, dok je istovremeno pokazano da je promenom SN moguće kontrolisati kinetiku bubrenja hidrogelova.

Malignant catarrhal fever (Coryza gangraenosa bovum)

Malignant catarrhal fever is a disease of cattle and other ruminants, which most often has a lethal outcome. The disease occurs sporadically and is very difficult to control. At a private mini cattle farm, the occurrence of malignant catarrhal fever was suspected on the grounds of anaemnestic data and results of clinical examinations. The owner said that, in addition to cattle, he also breeds sheep in a separate facility, but said these animals had not been in contact with the diseased cow. In the course of the disease, the characteristic symptoms developed so that the clinical diagnosis set earlier was subsequently confirmed. In addition to constantly elevated body temperature, changes in the eyes were observed very soon (congested blood vessels and capillaries of the white sclera with keratitis on both sides). In addition to photofobia and a copious discharge from the nasal cavities, the discharge was at first seromucous and later became mucopurrulent. In the later course of the disease, there was progressive loss of weight and exhaustion of the animal. Since therapy included, in addition to other medicines, also a glucocorticosteroid preparation, the animal aborted its fetus on the fifth day. A pathological-anatomical examination did not reveal any changes on the fetus. In spite of the applied therapy, the medical condition deteriorated from day to day, and the animal expired on the eighth day of the disease