Browsing by Author "Jančić, Jasna, član komisije"

Posebne mikromorfološke karakteristike vaskularizacije kolenog gangliona (ganglion geniculi), kao i mogući klinički značaj periganglijske i intraganglijske vaskularne mreže bili su prvi ciljevi ove studije...

Background: Mitochondriopathies (MCPs) are considered as diverse group of genetically caused diseases due to deficiencies of the energy production in mitochondria. MCPs can be expressed in many tissues, especially those with higher metabolic demands so they affect most commonly nervous system and muscles. MCPs are characterized by clinical heterogeneity presented by varioaus clinical phenotypes, occur at any age and.could be mild or severe. Besides nervous system and muscles, eye, heart, liver, kidney, bone marrow and other organs could be involved. The main cause of MCPs are genetic changes but interaction with environmental factors plays a role also. Mitochondrial function is controlled by genes located in both nuclear and mitochondrial genome. Mitochondrial genome is represented by maternally inherited mitochondrial DNA (mtDNA), which is considered as a genetic hotspot for MCPs. Molecules of mtDNA show 10–20 times higher mutational rate compared to nuclear genetic material, and could be affected by point mutations, larger deletions or even deplecion, all leading to MCPs. Estimated prevalence of MCPs is 1 in 8.000 to 20.000. Some examples of the disorders caused by pathogenic mtDNA mutations are: Leber hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), maternally inherited Leigh syndrome (LS), neuropathy, ataxia and retinitis pigmentosa (NARP), myoclonic epilepsy with ragged-red fibers (MERRF), etc. Genetics background of the pathogenic mtDNA mutations, represented by secondary mutations and mitochondrial haplogroups, affects penetrance and expressivitiy of MCPs. Geographic and/or ethnic specificity of this background emphasizes its role. Aim: The main aim of thic study was determination and characterisation of primary and secondary mutations of mtDNA in patients clinically diagnosed with MCPs. The majority of cases had LHON, but MELAS and other mitochondriopathies were included also. It was planned to detect the well-known LHON mutations m.3460G>A, m.11778G>A, and m.14484T>C, major MELAS mutation m.3243A>G and other mutations specific for MCPs in Serbian patients. Another objective was establishement of the specific genetic background with determination of mtDNA haplogroups of the respondents and construction of the corresponding phylogenetic tree. Finally, the aim was correlation between genotype and phenotype in MCPs patients. Material and methods: This study included total number of eleven unrelated Serbian subjects – probands diagnosed with MCPs and four their asymptomatic relatives. Probands were diagnosed in the Clinic for Neurology and Psychiatry for Children and Youth and Clinic of Neurology, Clinical Centre of Serbia, Belgrade. In all respondents full clinical examination was performed. Demographic data, habits and risk factors, past personal and familial history were evaluated. Family history for maternal relatives was clarified in detail. All molecular genetic analyses of mtDNA were performed in the Laboratory for genetic and molecular diagnostics of neurological diseases at the Clinic for Neurology, Clinical Centre of Serbia. The detection of mtDNA mutations was performed by direct Sanger sequencing of whole mitochondrial genome. Revised Cambridge Reference Sequence of human mtDNA was used for comparision. Prediction of mtDNA mutations‘ pathogenicity was done by in silico analysis using available softwares. MITOMASTER analysis was used for the determination of haplogroups and characterization of pathogenic variants. The phylogenetic tree was constructed according to mtDNA tree Build 17 nomenclature...

Although still debated about its definition and conceptualization, the healthrelated quality of life (HRQOL) concept is simply defined as the patient’s evaluation of the impact of a health condition and its treatment on daily life. HRQOL is a multidimensional construct that covers physical, emotional, mental, social, and behavioral components of well-being and functioning. HRQOL is possible to conceptualize through objective indicators. A great deal of attention has been paid to ensure reliable and valid HRQOL measurements through the development of questionnaires with sound psychometric properties. Continually from the past decade, HRQOL is more frequently used in prevention, treatment, and rehabilitation both, nationally and internationally. This requires that HRQOL measures are available across different nations/languages. With this in mind, questionnaires with good psychometric properties need to be simultaneously developed across different nations and cultures or, a slightly different but equally successful approach, the translation, subsequent analysis, and adaptation of existing and accepted measures into other languages is performed while considering aspects of the cultural settings. So far, cross-cultural adaptation of questionnaires has been recognized as one of the priority in HRQOL research. It is early recognized that HRQOL assessments have some specific characteristics when children and adolescents are considered. The development of pediatric HRQOL measurement followed specific pathways with several important issues: specific HRQOL domains, age and developmental characteristics, self- and proxy-rating, generic and disease specific approaches to assessments, and psychometric considerations. Up to date, no clear guidelines for the cross-cultural adaptation of pediatric HRQOL questionnaires were developed. The aim of this thesis was to operationalize a model of the cross-cultural adaptation of pediatric HRQOL questionnaires...

Migrena je šesti specifični uzrok onesposobljenosti širom sveta u adultnoj populaciji. Aura se javlja kod 20 % osoba koje boluju od migrene. Tokom migrenske aure javljaju se različiti vizuelni i senzitivni fenomeni, kao i poremećaji viših kortikalnih funkcija, što ukazuje na zahvaćenost različitih regiona cerebralnog korteksa. Iako je migrena sa aurom (MA) prevashodno funkcionalni poremećaj, koji je predstavljen talasom kortikalne depolarizacije/depresije kao biološkim supstratom bolesti, nedavna istraživanja pokazuju da se morfološke i mikrostrukturne promene mogu pronaći u mozgu kod osoba koje imaju MA. Uticaj debljine cerebralnog korteksa i mikrostrukturnih promena, međutim, na složenost migrenske aure nije poznata. Ove praznine u razumevanju patofizioloških mehanizama koji dovode do nastanka MA mogu se premostiti različitim neurovizuelizacionim tehnikama. CILJEVI: Ciljevi ove studije su višestruki: 1) da se proceni učestalost i vrste poremećaja viših kortikalnih funkcija koje se javljaju tokom vizuelne i/ili senzitivne aure, 2) da se proceni učestalost i klinički uticaj interiktalno detektovanih mikroembolijskih signala (MES) kod pacijenata koji boluju od migrene sa višim kortikalnim poremećajima (VKP) tokom aure, 3) da se istraže razlike u debljini cerebralnog korteksa između osoba koje imaju MA i zdravih ispitanika (ZI) i da se analizira moguća lokalizaciona povezanost između debljine korteksa i različitih oblika aure, i 4) da se istraži integritet bele moždane mase projekcionih, asocijativnih i komisuralnih nervnih vlakana kod osoba koje imaju MA, kao i da se opiše moguća razlika integriteta bele moždane mase u odnosu na kompleksnost migrenske aure. MATERIJALI I METODE: Ova studija se sastoji od četiri istraživanja u kojima su učestvovale različite kohorte koje su sačinjavale osobe koje imaju MA. Prvo, su kliničkim intervujom 60 osoba koje imaju MA dobijeni podaci o simptomima i demografskim podacima, a posebno o VKP tokom aure uz pomoć specijalno dizajniranog upitnika. Nakon toga, pacijenti su podeljeni u dve grupe, u odnosu na VKP, koje su upoređene u odnosu na demografske podatke i karakteristike aure. Zatim je istraživano prisustvo MES kod grupe sa VKP (VKP grupa), grupe bez VKP (Kontrolna grupa I), i ZI (Kontrolna grupa II). MES su detektovani transkranijalnim Dopplerom...

Увод: Дишенова мишићна дистрофија (ДМД) је најчешћа наследна болест мишића са почетком у дечјем добу. Варијабилност клиничког тока ДМД делимично је објашњена варијантама у модификујућим генима. Циљеви: Одређивање учесталости алела варијанти гена SPP1, LTBP4 и CD40 и испитивање њихове појединачне и удружене повезаности са клиничком прогресијом ДМД у групи покретних и непокретних болесника. Материјал и методе: Генотипизоване су варијанте у SPP1 - rs28357094 и CD40 - rs1883832, као и хаплотип у LTBP4 гену - rs2303729, rs1131620, rs1051303, rs10880, тестом алелне дискриминације, код 95 болесника. Мера исхода била је време губитка хода, односно постигнућа на моторним скалама током једногодишњег периода праћења. Појединачни ефекат варијанти процењен је анализама преживљавања, а удружени хијерархијском кластер анализом. Резултати: Оболели који су користили кортикостероидну (КС) терапију изгубили су кретање годину дана касније (p=0,021). Учесталост ређих алела за анализиране варијанте била је у складу са учесталошћу за европску популацију. Модификујући ефекат. варијанти SPP1 и CD40 и хаплотипова LTBP4 није описан коришћењем log-rang теста и мултиваријантне Cox регресионе анализе. Кластер анализа је открила две подгрупе са статистичким трендом у разлици у годинама у време губитка хода. У групи покретних болесника мањи пад вредности на моторним скалама имали су носиоци заштитне варијанте у испитиваним генима. Закључци: Модификујући ефекат SPP1, LTBP4 и CD40 на клинички ток ДМД није описан иако је кохорта била упоредива по типовима мутација у DMD гену, фреквенцији варијанти одабраних гена и позитивном ефекту КС терапије са другим европским кохортама. Кластер анализа може да идентификује подгрупе које носе комбинацију генетских варијанти које модификују узраст у време губитка хода.