Neželeni učinki radioterapije na možgane

There are numerous and often unpredictable side effects of radiotherapy on the brain. The damage can be direct or indirect, and becomes apparent acutely or even many years thereafter. The distinction between these forms is important since early side effects are predominantly reversible whereas late ones usually are not. The incidence of radiotherapy-induced side effects is hard to estimate due to the differing definitions and methodologies used in clinical studies. Nevertheless, the clinical picture often resembles the progression of pre-existent malignant disease. The mechanism underlying side effects of radiotherapy is mainly injury to glial cells and cerebral endothelial cells. The hippocampus is especially prone to radiation damage. The burden of radiation damage in a given individual is dependent upon many factors. Concomitant systemic and intrathecal chemotherapy adds significantly to neurotoxicity. Diagnosing side effects of radiotherapy can be a daunting task since the time interval between radiotherapy and the occurrence of neurological side effects is variable. What is more, the clinical picture can resemble metastatic, paraneoplastic or other neurological disease. It is therefore of crucial importance to be aware of the fact that the clinical picture can be ascribed to side effects of radiotherapy only after other possible reasons (mainly tumor progression) have been effectively ruled out. The article entails a broad spectrum of direct and indirect radiotherapyinduced consequences on the brain. Acute encephalopathy is connected to blood-brain barrier disruption. Early-delayed encephalopathy is caused by demyelination. Late-delayed encephalopathy is represented mainly by radiation necrosis. Cognitive decline as a consequence of radiotherapy is still a matter of hot debate.Neželeni učinki radioterapije na možgane so številni in pogosto nepredvidljivi. Lahko gre za neposredno ali posredno okvaro možganov. Okvara se lahko pojavi akutno ali več tednov, mesecev ali celo let po končani radioterapiji. Ločevanje med temi oblikami je pomembno, saj so zgodnji zapleti navadno reverzibilni, pozni pa se večinoma ne popravijo. Incidenco neželenih učinkov radioterapije na možgane je težko oceniti. Razlogi za to so v različnih opredelitvah in metodoloških razlikah v raziskavah ter v klinični sliki, ki se pogosto prekriva z napredovanjem osnovne maligne bolezni. Med mehanizmi radiacijske okvare možganov je v ospredju okvara celic glije in možganskih endotelijskih celic. Za radiacijsko okvaro je zlasti občutljiv hipokampus. Obseg okvare možganov je odvisen od številnih dejavnikov. Dodatna sistemska ali intratekalna kemoterapija pomembno poveča nevrotoksičnost. Diagnosticiranje neželenih učinkov radioterapije na možgane je težavno, saj je časovni interval med radioterapijo in pojavom nevroloških simptomov precej variabilen, klinična slika pa lahko posnema metastatsko, paraneoplastično ali drugo nevrološko bolezen. Zavedati se je treba, da klinično sliko lahko pripišemo neželenim učinkom radioterapije na možgane šele po izključitvi drugih vzrokov. V članku opisujeva različne klinične oblike neposredne in posredne radiacijske okvare možganov. Pri akutni encefalopatiji ima pomembno vlogo okvara krvno-možganske pregrade. Pri zgodnji odloženi encefalopatiji je pomembna demielinizacija, pri pozni odloženi encefalopatiji pa radiacijska nekroza. O kognitivnem upadu kot posledici radioterapije so mnenja še vedno deljena

Side effects of radiotherapy on the brain

Neželeni učinki radioterapije na možgane so številni in pogosto nepredvidljivi. Lahko gre za neposredno ali posredno okvaro možganov. Okvara se lahko pojavi akutno ali več tednov, mesecev ali celo let po končani radioterapiji. Ločevanje med temi oblikami je pomembno, saj so zgodnji zapleti navadno reverzibilni, pozni pa se večinoma ne popravijo. Incidenco neželenih učinkov radioterapije na možgane je težko oceniti. Razlogi za to so v različnih opredelitvah in metodoloških razlikah v raziskavah ter v klinični sliki, ki se pogosto prekriva z napredovanjem osnovne maligne bolezni. Med mehanizmi radiacijske okvare možganov je v ospredju okvara celic glije in možganskih endotelijskih celic. Za radiacijsko okvaro je zlasti občutljiv hipokampus. Obseg okvare možganov je odvisen od številnih dejavnikov. Dodatna sistemska ali intratekalna kemoterapija pomembno poveča nevrotoksičnost. Diagnosticiranje neželenih učinkov radioterapije na možgane je težavno, saj je časovni interval med radioterapijo in pojavom nevroloških simptomov precej variabilen, klinična slika pa lahko posnema metastatsko, paraneoplastično ali drugo nevrološko bolezen. Zavedati se je treba, da klinično sliko lahko pripišemo neželenim učinkom radioterapije na možgane šele po izključitvi drugih vzrokov. V članku opisujeva različne klinične oblike neposredne in posredne radiacijske okvare možganov. Pri akutni encefalopatiji ima pomembno vlogo okvara krvno-možganske pregrade. Pri zgodnji odloženi encefalopatiji je pomembna demielinizacija, pri pozni odloženi encefalopatiji pa radiacijska nekroza. O kognitivnem upadu kot posledici radioterapije so mnenja še vedno deljena.There are numerous and often unpredictable side effects of radiotherapy on the brain. The damage can be direct or indirect, and becomes apparent acutely or even many years thereafter. The distinction between these forms is important since early side effects are predominantly reversible whereas late ones usually are not. The incidence of radiotherapy-induced side effects is hard to estimate due to the differing definitions and methodologies used in clinical studies. Nevertheless, the clinical picture often resembles the progression of pre-existent malignant disease. The mechanism underlying side effects of radiotherapy is mainly injury to glial cells and cerebral endothelial cells. The hippocampus is especially prone to radiation damage. The burden of radiation damage in a given individual is dependent upon many factors. Concomitant systemic and intrathecal chemotherapy adds significantly to neurotoxicity. Diagnosing side effects of radiotherapy can be a daunting task since the time interval between radiotherapy and the occurrence of neurological side effects is variable. What is more, the clinical picture can resemble metastatic, paraneoplastic or other neurological disease. It is therefore of crucial importance to be aware of the fact that the clinical picture can be ascribed to side effects of radiotherapy only after other possible reasons (mainly tumor progression) have been effectively ruled out. The article entails a broad spectrum of direct and indirect radiotherapyinduced consequences on the brain. Acute encephalopathy is connected to blood-brain barrier disruption. Early-delayed encephalopathy is caused by demyelination. Late-delayed encephalopathy is represented mainly by radiation necrosis. Cognitive decline as a consequence of radiotherapy is still a matter of hot debate

How Can We Advance Integrative Biology Research in Animal Science in 21st Century?:Experience at University of Ljubljana from 2002 to 2022

In this perspective analysis, we strive to answer the following question: how can we advance integrative biology research in the 21st century with lessons from animal science? At the University of Ljubljana, Biotechnical Faculty, Department of Animal Science, we share here our three lessons learned in the two decades from 2002 to 2022 that we believe could inform integrative biology, systems science, and animal science scholarship in other countries and geographies. Cultivating multiomics knowledge through a conceptual lens of integrative biology is crucial for life sciences research that can stand the test of diverse biological, clinical, and ecological contexts. Moreover, in an era of the current COVID-19 pandemic, animal nutrition and animal science, and the study of their interactions with human health (and vice versa) through integrative biology approaches hold enormous prospects and significance for systems medicine and ecosystem health

Brazilian cave heritage under siege

info:eu-repo/semantics/publishe

SALES PROMOTION IN RIMSKE TERME

Naloga obsega jasno opredeljene splošne pojme o pospeševanju prodaje, osnovah marketinškega komuniciranja in opis podjetja, njihove dejavnosti ter metode pospeševanja v podjetju. Pospeševanje prodaje velja za eno ključnih orodij marketinškega komuniciranja, kateremu podjetja dan danes namenjajo vse več sredstev. Da le to dobro funkcionira, mora potekati odlična medsebojna komunikacija, ki danes predstavlja skorajda najpomembnejšo funkcijo vsakega podjetja, saj velja, če je komunikacija dobra, je posledično zagotovljen tudi uspeh. Da bi kupca čimbolj pritegnili, podjetja uporabljajo različne pristope, da ga prepričajo oz. pritegnejo k prvemu nakupu. Poznamo več različnih metod od kuponov in nagradnih iger pa tja do brezplačnih preizkusov izdelkov, daril in posebnih popustov. Poleg samega pospeševanja prodaje, je v diplomskem delu tudi govor o zdraviliškem turizmu in wellness-u, saj smatramo, da imajo zdraviliški centri in wellness centri že ustaljeno in pomembno vlogo v slovenskem turizmu. Sam zdraviliški turizem prištevamo med najstarejše oblike turizma, saj so že stari Rimljani, obiskovali terme zaradi toplih vrelcev, počitka in boljšega počutja.This thesis comprises clearly defined general notions on sales promotions, basics of marketing communication and description of the company, their activities and methods of promotion within the company. Sales promotion is considered to one of the key tools of marketing communication, which these days companies devoitng more and more resources. That this functions well, it must be carried out excellent interpersonal communication, which is today almost one of the most important functions of each company. If the communication is good is consequently also guaranteed success. In order to attract a customer, companies use different approaches to convince him or attract to the first purchase. There are several different methods, from coupons to coupons and sweepstakes, to free tasting products, gifts and special discounts. In addition to the sales promotion, the thesis also talks about health tourism and wellness centers, because these days we believe that health centers and wellness centers have an important role in Slovenian tourism. Health tourism belongs among the oldest forms of tourism as the ancient Romans have visited spas because of hot springs, rest and better feeling

Effect of cocaprin and macrocypin on Listeria biofilm

Povzetek: Listeria monocytogenes je Gram pozitivna patogena bakterija, ki povzroča listeriozo. Pri delu smo uporabili njej sorodno nepatogeno vrsto Listeria innocua, ki se pogosto uporablja kot modelni organizem za L. monocytogenes. Bakterije rastejo v obliki biofilma, ki jim omogoča rast na različnih površinah in ima pomembno vlogo pri preživetju bakterij v okolju. Biofilmi listerije so običajno v literaturi opisani kot monoslojni, pri našem delu pa smo opazili, da tvori tudi dvosloj in večslojne strukture, podobne piramidam. Proteini iz gob predstavljajo razmeroma neraziskano skupino proteinov z edinstvenimi lastnostmi. Med njimi izstopajo inhibitorji peptidaz in lektini, med katerimi sta tudi kokaprin in makrocipin. Kokaprin (KKP1) je majhen neraziskan protein izoliran iz gobe Coprinopsis cinerea in deluje kot inhibitor cisteinskih in aspartatnih peptidaz ter lektin. Makrocipin (Mcp1) pa je inhibitor cisteinskih peptidaz iz gobe Macrolepiota procera. V bakterijskem ekspresijskem sistemu smo pripravili rekombinantne proteine Mcp1, KKP1 in štiri mutante KKP1 (KKP1-N22R, KKP1-D47R, KKP1-FH32EE, KKP1-G13E). Z merjenjem inhibitorne aktivnosti za encim papain smo potrdili inhibitorno aktivnost makrocipina, z encimoma papain in pepsin pa smo preverili inhibitorno aktivnost za KKP1 in njegove mutante. Med njimi je izstopal mutant KKP1-N22R, pri katerem smo uspešno spremenili reaktivno mesto za inhibicijo papaina. S tem smo nakazali, da ima kokaprin ločena mesta za inhibicijo cisteinskih in aspartatnih peptidaz. Z analizo nativne poliakrilamidne gelske elektroforeze smo pokazali, da se KKP1 in njegovi mutanti povezujejo v oligomere. Preverili smo vpliv izoliranih proteinov iz gob na biofilm bakterije L. innocua, za kar smo predhodno uspešno pripravili bakterije, ki so izražale različne reporterske proteine, od katerih se je najbolje izkazal DsRED Express. Poleg tega smo za detekcijo divjega tipa bakterij L. innocua preizkusili različne označevalce in barvila. Za najbolj uporabno se je izkazalo komercialno barvilo Mycolight Red, ki se veže na DNA bakterij. S preverjanjem, ali izbrani proteini iz gob vplivajo na razvoj biofilma bakterije L. innocua, smo ugotovili, da tako kokaprin kot makrocipin povzročita zmanjšano adhezijo bakterij na substrat. Opazili smo tudi viden učinek kokaprina na razbijanje statičnega biofilma in učinek makrocipina na razbijanje dinamičnega biofilma. Na adhezijo bakterij na substrat in na razbijanje zrelega statičnega biofilma imajo močnejši vpliv od KKP1 tri njegovi mutanti KKP1-N22R, KKP1-FH32EE in KKP1-G13E. Ti spremenjeni aminokislinski ostanki se nahajajo na isti strani KKP1, zato sklepamo, da se tam nahaja mesto, ki je pomembno za vezavo KKP1 na bakterije L. innocua. Tako kokaprin kot makrocipin torej vplivata na tvorbo biofilma bakterije L. innocua, zato bi bilo smiselno njun vpliv preveriti tudi na patogeno vrsto L. monocytogenes, ki predstavlja velik zdravstven problem. Če se vpliv izbranih proteinov iz gob na tvorbo biofilma patogene bakterije potrdi, bi jih lahko uporabili za nadaljnje študije in razvoj novih protimikrobnih snovi ali celo zdravil za zdravljenje okužb z listerijo.Abstract Listeria monocytogenes is a Gram-positive pathogenic bacterium that causes listeriosis. We used the related non-pathogenic species Listeria innocua, which is often used as a model organism for L. monocytogenes. Bacteria grow in the form of a biofilm and resist different types of stress, and plays an important role in the survival of bacteria in the environment. Listeria biofilms are usually described as monolayers in the literature. In our work, we observed that they also form bilayer and multilayer pyramid-like structures. Fungal proteins represent a relatively unexplored group of proteins with unique properties. These include peptidase inhibitors and lectins, including cocaprin and macrocypin. Cocaprin (KKP1) is a small unexplored protein isolated from Coprinopsis cinerea that acts as an inhibitor of cysteine and aspartic peptidases. Macrocypin (Mcp1) is an inhibitor of cysteine peptidases from Macrolepiota procera. The recombinant proteins Mcp1, KKP1 and four KKP1 mutants (KKP1-N22R, KKP1-D47R, KKP1-FH32EE, KKP1-G13E) were produced in a bacterial expression system. By measuring the inhibitory activity for the enzyme papain, we confirmed the activity for macrocypin, and using the enzymes papain and pepsin, we analysed the inhibitory activity of KKP1 and its mutants. Among them, the mutant KKP1-N22R stood out, in which we successfully changed the reactive site for papain inhibition. This suggests that cocaprin has separate sites for inhibition of cysteine and aspartic peptidases. Native polyacrylamide gel electrophoresis analysis showed that KKP1 and its mutants form oligomers. We investigated the effect of isolated fungal proteins on the biofilm of L. innocua, for which we had previously successfully produced bacteria expressing different reporter proteins, of which DsRED Express proved to be the best. We also tested various markers and dyes for the detection of wild-type L. innocua. The commercial dye Mycolight Red, which binds to bacterial DNA, proved most useful. When investigating whether selected fungal proteins affect L. innocua biofilm development, we found that both cocaprin and macrocypin caused decrased adhesion of bacteria to the substrate. However, we also observed a visible effect of cocaprin on the degradation of static biofilms and the effect of macrocypin on the degradation of dynamic biofilms. Bacterial adhesion to the substrate and degradation of the mature static biofilm were more affected by the three mutants KKP1-N22R, KKP1-FH32EE, and KKP1-G13E than by KKP1. These altered amino acid residues are located on the same side of KKP1, suggesting that there is a site important for binding to L. innocua bacteria. Both cocaprin and macrocypin affect the formation of L. innocua biofilm, so it is worth analysing their effect on the pathogenic species L. monocytogenes, which is a major health problem. If the effect of selected fungal proteins on biofilm formation of pathogenic bacteria were confirmed, they could be used for further studies and development of new antimicrobial agents targeting biofilms or even drugs to treat listeriosis infections

Is it possible to predict clonal thrombocytosis in triple-negative patients with isolated thrombocytosis based only on clinical or blood findings?

JAK2, MPL, and CALR mutations define clonal thrombocytosis in about 90% of patients with sustained isolated thrombocytosis. In the remainder of patients (triple-negative patients) diagnosing clonal thrombocytosis is especially difficult due to the different underlying conditions and possible inconclusive bone marrow biopsy results. The ability to predict patients with sustained isolated thrombocytosis with a potential clonal origin has a prognostic value and warrants further examination. The aim of our study was to define a non-invasive clinical or blood parameter that could help predict clonal thrombocytosis in triple-negative patients. We studied 237 JAK2 V617-negative patients who were diagnosed with isolated thrombocytosis and referred to the haematology service. Sixteen routine clinical and blood parameters were included in the logistic regression model which was used to predict the type of thrombocytosis (reactive/clonal). Platelet count and lactate dehydrogenase (LDH) were the only statistically significant predictors of clonal thrombocytosis. The platelet count threshold for the most accurate prediction of clonal or reactive thrombocytosis was 449 × 10$^9$/L. Other tested clinical and blood parameters were not statistically significant predictors of clonal thrombocytosis. The level of LDH was significantly higher in CALR-positive patients compared to CALR-negative patients. We did not identify any new clinical or blood parameters that could distinguish clonal from reactive thrombocytosis. When diagnosing clonal thrombocytosis triple-negative patients are most likely to be misdiagnosed. Treatment in patients with suspected triple-negative clonal thrombocytosis should not be delayed if cardiovascular risk factors or pregnancy coexist, even in the absence of firm diagnostic criteria. In those cases the approach “better treat more than less” should be followed