Silent brain infarct

Akutni infarkt mozga svojim nastupom i simptomima uzrokuje relativno jasnu i prepoznatljivu kliničku sliku, no postoje kronične pojedinačne i/ili difuzne ishemične lezije mozga koje su klinički asimptomatske i duže vremena se ne prepoznaju. Termin tihi infarkt mozga često se koristi za opis infarkta mozga koji se slučajno utvrdi u osoba koje nikad ranije u svojoj povijesti bolesti nisu imale kliničke simptome tranzitorne ishemijske atake ili moždanog udara. Može ga se utvrditi obdukcijom ili neuroradiološkim pretragama, kompjutoriziranom tomografijom i magnetskom rezonancijom mozga. Radi se najčešće o malom infarktu u dubokim subkortikalnim regijama mozga i morfološki je sličan simptomatskom lakunarnom infarktu. Lakunarna ishemična lezija mozga posljedica je okluzije duboke, penetrantne arterije u čijoj se osnovi uglavnom nalazi hipertenzivna moždana mikroangiopatija. Tihom infarktu mozga posljednje se desetljeće pridaje velika pažnja jer su studije pokazale da prisutnost tihog infarkta mozga dvostruko povećava rizik nastanka simptomatskog moždanog udara i demencije. U ovom preglednom članku prikazujemo epidemiologiju, patofiziološka obilježja, čimbenike rizika i moguće posljedice tihog infarkta mozga.With its onset and symptoms the acute brain stroke causes relatively clear and recognizable clinical features. However, there are chronic, single and/or diffuse ischemic brain lesions which are clinically asymptomatic and which take longer to recognize. The term ”silent brain infarct” is frequently used to describe the brain infarct which is determined with the autopsy by chance or which could be determined with computerized tomography. Such brain infarct could also be determined using the brain magnetic resonance imaging on people who never before had clinical symptoms transient ischemic attack or brain stroke in their lives. For the most of the time this is about small infarct in deep sub-cortical brain regions. It is morphologically similar to symptomatic lacunar infarct. Lacunar ischemic brain lesion is the consequence of the deep, perforating artery occlusion. Its base is mainly the hypertensive brain microangiopathy. The silent brain infarct is given great attention in the last decade because the studies show the silent brain infarct presence doubles the symptomatic brain stroke and dementia risk. In this review we show the epidemiology, the pathophysiologic attributes, the risk factors and possible silent brain infarct consequences

Silent brain infarct

Akutni infarkt mozga svojim nastupom i simptomima uzrokuje relativno jasnu i prepoznatljivu kliničku sliku, no postoje kronične pojedinačne i/ili difuzne ishemične lezije mozga koje su klinički asimptomatske i duže vremena se ne prepoznaju. Termin tihi infarkt mozga često se koristi za opis infarkta mozga koji se slučajno utvrdi u osoba koje nikad ranije u svojoj povijesti bolesti nisu imale kliničke simptome tranzitorne ishemijske atake ili moždanog udara. Može ga se utvrditi obdukcijom ili neuroradiološkim pretragama, kompjutoriziranom tomografijom i magnetskom rezonancijom mozga. Radi se najčešće o malom infarktu u dubokim subkortikalnim regijama mozga i morfološki je sličan simptomatskom lakunarnom infarktu. Lakunarna ishemična lezija mozga posljedica je okluzije duboke, penetrantne arterije u čijoj se osnovi uglavnom nalazi hipertenzivna moždana mikroangiopatija. Tihom infarktu mozga posljednje se desetljeće pridaje velika pažnja jer su studije pokazale da prisutnost tihog infarkta mozga dvostruko povećava rizik nastanka simptomatskog moždanog udara i demencije. U ovom preglednom članku prikazujemo epidemiologiju, patofiziološka obilježja, čimbenike rizika i moguće posljedice tihog infarkta mozga.With its onset and symptoms the acute brain stroke causes relatively clear and recognizable clinical features. However, there are chronic, single and/or diffuse ischemic brain lesions which are clinically asymptomatic and which take longer to recognize. The term ”silent brain infarct” is frequently used to describe the brain infarct which is determined with the autopsy by chance or which could be determined with computerized tomography. Such brain infarct could also be determined using the brain magnetic resonance imaging on people who never before had clinical symptoms transient ischemic attack or brain stroke in their lives. For the most of the time this is about small infarct in deep sub-cortical brain regions. It is morphologically similar to symptomatic lacunar infarct. Lacunar ischemic brain lesion is the consequence of the deep, perforating artery occlusion. Its base is mainly the hypertensive brain microangiopathy. The silent brain infarct is given great attention in the last decade because the studies show the silent brain infarct presence doubles the symptomatic brain stroke and dementia risk. In this review we show the epidemiology, the pathophysiologic attributes, the risk factors and possible silent brain infarct consequences

Silent brain infarct

Akutni infarkt mozga svojim nastupom i simptomima uzrokuje relativno jasnu i prepoznatljivu kliničku sliku, no postoje kronične pojedinačne i/ili difuzne ishemične lezije mozga koje su klinički asimptomatske i duže vremena se ne prepoznaju. Termin tihi infarkt mozga često se koristi za opis infarkta mozga koji se slučajno utvrdi u osoba koje nikad ranije u svojoj povijesti bolesti nisu imale kliničke simptome tranzitorne ishemijske atake ili moždanog udara. Može ga se utvrditi obdukcijom ili neuroradiološkim pretragama, kompjutoriziranom tomografijom i magnetskom rezonancijom mozga. Radi se najčešće o malom infarktu u dubokim subkortikalnim regijama mozga i morfološki je sličan simptomatskom lakunarnom infarktu. Lakunarna ishemična lezija mozga posljedica je okluzije duboke, penetrantne arterije u čijoj se osnovi uglavnom nalazi hipertenzivna moždana mikroangiopatija. Tihom infarktu mozga posljednje se desetljeće pridaje velika pažnja jer su studije pokazale da prisutnost tihog infarkta mozga dvostruko povećava rizik nastanka simptomatskog moždanog udara i demencije. U ovom preglednom članku prikazujemo epidemiologiju, patofiziološka obilježja, čimbenike rizika i moguće posljedice tihog infarkta mozga.With its onset and symptoms the acute brain stroke causes relatively clear and recognizable clinical features. However, there are chronic, single and/or diffuse ischemic brain lesions which are clinically asymptomatic and which take longer to recognize. The term ”silent brain infarct” is frequently used to describe the brain infarct which is determined with the autopsy by chance or which could be determined with computerized tomography. Such brain infarct could also be determined using the brain magnetic resonance imaging on people who never before had clinical symptoms transient ischemic attack or brain stroke in their lives. For the most of the time this is about small infarct in deep sub-cortical brain regions. It is morphologically similar to symptomatic lacunar infarct. Lacunar ischemic brain lesion is the consequence of the deep, perforating artery occlusion. Its base is mainly the hypertensive brain microangiopathy. The silent brain infarct is given great attention in the last decade because the studies show the silent brain infarct presence doubles the symptomatic brain stroke and dementia risk. In this review we show the epidemiology, the pathophysiologic attributes, the risk factors and possible silent brain infarct consequences

Association of lipid peroxidation product 4-hydroxynonenal with post-traumatic stress disorder

Repeated activation of the hypothalamic-pituitary-adrenal axis system, sleep disturbances, and other symptoms related to posttraumatic stress disorder (PTSD) elevate reactive oxygen species, increase inflammation, and accelerate cellular aging, leading to neuroprogression and cognitive decline. However, there is no information about possible involvement of 4-hydroxynonenal (4-HNE), the product of lipid peroxidation associated with stress-associated diseases, in the complex etiology of PTSD. Therefore, the aim of this study was to compare the plasma levels of 4-HNE between war veterans with PTSD (n = 62) and age-, sex- and ethnicity- matched healthy control subjects (n = 58) in order to evaluate the potential of HNE-modified proteins as blood-based biomarker of PTSD. The genuine 4-HNE-Enzyme-Linked Immunosorbent Assay (HNE-ELISA), based on monoclonal antibody specific for HNE-histidine (HNE-His) adducts, was used to determine plasma HNE-protein conjugates. Our results revealed significantly elevated levels of 4-HNE in patients with PTSD. Moreover, the accumulation of plasma 4-HNE seems to increase with aging but in a negative correlation with BMI, showing specific pattern of change for individuals diagnosed with PTSD. These findings suggest that oxidative stress and altered lipid metabolism reflected by increase of 4-HNE might be associated with PTSD. If confirmed with further studies, elevated 4-HNE plasma levels might serve as a potential biomarker of PTSD

Systemic thrombolysis for acute ischemic stroke treatment

Unatoč činjenici da je ishemijski moždani udar zbog visoke smrtnosti i invalidnosti velik javnozdravstveni problem, do pojave trombolitičke terapije nije postojao specifičan lijek za rekanalizaciju okludirane krvne žile. Tromboliza rekombiniranim tkivnim aktivatorom plazminogena (rt-PA) dokazala je svoju učinkovitost u nizu studija i za sada je jedini odobreni lijek za liječenje ishemijskog moždanog udara. Radi poboljšanja ishoda liječenja potrebno je liječenje provoditi u specijaliziranim odjelima – jedinicama za liječenje moždanog udara, koje uz pravovremeno prepoznavanje moždanog udara i žurno postavljanje dijagnoze predstavljaju preduvjet za brzo započinjanje terapije u cilju rane rekanalizacije krvne žile i reperfuzije moždanog parenhima. Ovakav pristup zbrinjavanju bolesnika s ishemijskim moždanim udarom omogućava ponovno uspostavljanje cirkulacije u ishemijskom području mozga, dok je oštećenje neurona reverzibilno, što u konačnici poboljšava ishod liječenja.In spite of the fact that ischemic stroke is an important public health problem because of high mortality and disability, until thrombolysis was established as a standard treatment for ischemic stroke there was no specific therapy for recanalization of occluded blood vessels. Efficacy of thrombolysis with recombinant tissue plasminogen activator (rt-PA) has been proven in a number of studies and currently is only approved therapy for acute ischemic stroke treatment. In order to improve outcome, ischemic stroke patients need to be treated in specialized units – stroke units. After early recognitions of stroke symptoms and urgent diagnosis these units are a prerequisite for an urgent start of therapy with purpose of early recanalization of blood vessels and reperfusion of brain parenchyma. This approach in management of ischemic stroke patients makes it possible for circulation to be restored in the ischemic region of the brain while neurons are still reversible damaged leading to an improved outcome at the end

Inorganic fullerene-like nanoparticles and nanotubes of tungsten disulfide as reinforcement of carbon-epoxy composites

A possibility was examined to enhance carbon-epoxy laminated composite mechanical properties by introducing a small concentration of reinforcing nanostructures - multi-wall onion-shaped fullerene-like nanoparticles of tungsten disulfide IF-WS2, and its multi-layer hollow nanotubes, INT-WS2, both known for their outstanding thermal, chemical, and mechanical resistance. Composite structures were prepared using a unidirectional prepreg of strong carbon fibers and epoxy resin, poly (vinyl butyral) solution in ethanol with ultrasonically dispersed WS2 nanostructures in it. Particle size analysis has been performed to evaluate the quality of IF-WS2 nanoparticles. SEM/EDS analysis was applied to observe the nanostructures, their dispersion in the composite, and the fracture zone after mechanical resistance tests of the prepared composite samples. Thorough mechanical tests were performed on a set of specimens with different fiber orientations: tensile test, bending test, and interlaminar shear test. The encouraging results were obtained, indicating that these newly designed light-weight composites are applicable for the automotive and nautical industry, unmanned aerial vehicles, and military aircrafts

Inorganic fullerene-like nanoparticles and nanotubes of tungsten disulfide as reinforcement of carbon-epoxy composites

A possibility was examined to enhance carbon-epoxy laminated composite mechanical properties by introducing a small concentration of reinforcing nanostructures - multi-wall onion-shaped fullerene-like nanoparticles of tungsten disulfide IF-WS2, and its multi-layer hollow nanotubes, INT-WS2, both known for their outstanding thermal, chemical, and mechanical resistance. Composite structures were prepared using a unidirectional prepreg of strong carbon fibers and epoxy resin, poly (vinyl butyral) solution in ethanol with ultrasonically dispersed WS2 nanostructures in it. Particle size analysis has been performed to evaluate the quality of IF-WS2 nanoparticles. SEM/EDS analysis was applied to observe the nanostructures, their dispersion in the composite, and the fracture zone after mechanical resistance tests of the prepared composite samples. Thorough mechanical tests were performed on a set of specimens with different fiber orientations: tensile test, bending test, and interlaminar shear test. The encouraging results were obtained, indicating that these newly designed light-weight composites are applicable for the automotive and nautical industry, unmanned aerial vehicles, and military aircrafts

Strategije ujemanja deležnika s koordiniranimi osebki v bosanskem/hrvaškem/srbskem jeziku

In this paper, we demonstrate that Bosnian/Croatian/Serbian (BCS), like Slovenian, has three distinct strategies of subject-predicate agreement when the subject consists of conjoined noun phrases: 1. agreement with the maximal projection – a Boolean Phrase (&P), 2. agreement with the conjunct which is closest to the participle, and 3. agreement with the conjunct which is hierarchically the highest. In order to test the initial hypothesis that there are three agreement strategies, we conducted a controlled experimental study of the morphosyntax of agreement between conjoined subjects and participles in BCS, which consisted of an oral production experiment and a written production experiment. These experiments revealed a high presence of default agreement and closest  conjunct agreement in the language. 50% of preverbal conjoined phrases elicited the default masculine agreement and 95% of postverbal conjoined noun phrases elicited the closest conjunct agreement. However, the bulk of the analysis focused on the possibility of treating the highest conjunct agreement (HCA) as a legitimate agreement strategy. 7% of all of the agreement forms in the subject preverbal (SV) examples demonstrated HCA. These figures increased to 13% if individual conditions were considered. Last conjunct agreement (LCA) for subject postverbal (VS) examples, on the other hand, was only present in 1% of the examples. For this reason, we classified them as performance errors and refuted LCA as an agreement strategy. These results are contrary to Bošković’s findings (2009), in which he does not acknowledge HCA as a legitimate strategy, however, our results do confirm the findings of Marušič et al. (2015).V članku pokažemo, da ima bosanski/hrvaški/srbski jezik (BHS) tako kot slovenščina tri strategije ujemanja med osebkom in predikatom, ko je osebek koordinirana samostalniška zveza: 1. ujemanje z maksimalno projekcijo – Boolejeva zveza (&P); 2. ujemanje s koordinirano prvino, ki je bližja deležniku; 3. ujemanje s koordinirano prvino, ki je najvišje v hierarhiji. Da bi preverili podmeno o treh strategijah ujemanja, smo izvedli kontrolirano eksperimentalno študijo oblikoslovno-skladenjskega ujemanja med koordiniranimi osebki in deležniki v BHS, ki je vključevala eksperimenta z govorjenim in pisnim jezikom. Eksperimenta sta pokazala visoko prisotnost privzetega ujemanja in ujemanja z najbližjo koordinirano prvino v osebku. Petdeset odstotkov predglagolskih koordiniranih zvez je pokazalo privzeto ujemanje z moško obliko, petindevetdeset odstotkov zaglagolskih koordiniranih samostalniških zvez pa se je ujemalo po načelu najbližje koordinirane prvine. Analiza je bila v največji meri osredinjena na ustreznost ujemanja s koordinirano prvino, ki je najvišje v hierarhiji (HCA). Slednja se je pojavila v sedmih odstotkih oblik, kjer je bil osebek v predglagolskem položaju. Odstotek naraste na 13, če upoštevamo posamezne pogoje. Ujemanje z zadnjo koordinirano prvino pri zaglagolskih osebkih (LCA) pa je bilo prisotno le v enem odstotku primerov, zato smo jih opredelili kot napake v rabi jezika in zavrnili LCA kot ustrezno strategijo ujemanja. Rezultati nasprotujejo študiji Boškovića (2009), ki zavrača HCA kot ustrezno strategijo, potrjujejo pa izsledke Marušiča et al. (2015)

Machine learning prioritizes synthesis of primaquine ureidoamides with high antimalarial activity and attenuated cytotoxicity

Primaquine (PQ) is a commonly used drug that can prevent the transmission of Plasmodium falciparum malaria, however toxicity limits its use. We prepared five groups of PQ derivatives: amides 1a-k, ureas 2a-k, semicarbazides 3a,b, acylsemicarbazides 4a-k and bis-ureas 5a-v, and evaluated them for antimalarial activity in vitro against the erythrocytic stage of P. falciparum NF54. Particular substituents, such as trityl (in 2j and 5r) and methoxybenzhydryl (in 3b and 5v) were associated with a favorable cytotoxicity-to-activity ratio. To systematically link structural features of PQ derivatives to antiplasmodial activity, we performed a quantitative structure-activity relationship (QSAR) study using the Support Vector Machines machine learning method. This yielded a highly accurate statistical model (R2 = 0.776 in cross-validation), which was used to prioritize novel candidate compounds. Seven novel PQ-ureidoamides 10a-g were synthesized and evaluated for activity, highlighting the benzhydryl ureidoamides 10e and 10f derived from p-chlorophenylglycine. Further experiments on human cell lines revealed that 10e and 10f are an order of magnitude less toxic than PQ in vitro while having antimalarial activity indistinguishable from PQ. The toxicity profile of novel compounds 10 toward human cells was particularly favorable when the glucose-6-phosphate dehydrogenase (G6PD) was inhibited, while toxicity of PQ was exacerbated by G6PD inhibition. Our work therefore highlights promising lead compounds for the development of effective antimalarial drugs that may also be safer for G6PD-deficient patients. In addition, we provide computational inferences of antimalarial activity and cytotoxicity for thousands of PQ-like molecular structures