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    BRAIN AND SPINAL CORD ORGANOIDS IN NEURODEGENERATIVE DISEASE RESEARCH

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    Organoidi mozga i leđne moždine predstavljaju inovativne trodimenzionalne stanične strukture dobivene iz ljudskih matičnih stanica koje vjerno oponašaju funkciju središnjeg živčanog sustava. U posljednjem desetljeću razvijeni su modeli za proučavanje neurodegenerativnih bolesti poput Alzheimerove bolesti, Parkinsonove bolesti i amiotrofične lateralne skleroze (ALS). Njihova sposobnost samorganizacije i diferencijacije u više tipova stanica, uključujući neurone i glija stanice, omogućuje bolje razumijevanje patoloških procesa, kao i testiranje novih potencijalnih terapija u uvjetima sličnima ljudskome organizmu. Organoidi mozga omogućuju stvaranje modela različitih regija mozga, poput korteksa ili srednjeg mozga, dok organoidi leđne moždine omogućuju stvaranje motoričkih neurona i analizu neuro-mišićne degeneracije. Unatoč brojnim prednostima, ova tehnologija i dalje ima neka određena ograničenja, kao što su nedostatak vaskularizacije, nedostatak imunoloških komponenti i ograničenje zrelosti stanica. Ipak, daljnjim razvojem i poboljšanjem funkcionalnosti organoida, otvara se mogućnost za precizniju personaliziranu medicinu i razvoj učinkovitijih terapija za neurodegenerativne bolesti.The organoids of the brain and spinal cord represent the innovative three -dimensional cellular structures obtained from human stem cells that faithfully mimic the function of the central nervous system. In the last decade, models for the study of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amiotrophic lateral sclerosis (ALS) have been developed. Their ability to self -organize and differentiation in multiple cell types, including neurons and glia cells, allows for a better understanding of pathological processes, as well as testing new potential therapies in conditions similar to the human body. Brain organoids allow models of different brain regions, such as a cortex or medium brain, while the organoids of the spinal cord allow the formation of motor neurons and analyzing neuro-muscular degeneration. Despite numerous advantages, this technology still has some certain restrictions, such as lack of vascularization, lack of immune components and restriction of cell maturity. However, with further development and improvement of organic functionality, there is an opportunity for more accurate personalized medicine and the development of more effective therapies for neurodegenerative diseases

    The effect of aging on hearing outcomes after sudden sensorineural hearing loss (SSNHL): A retrospective study

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    Objectives: To analyze the effect of aging on hearing outcomes following treatment for sudden sensorineural hearing loss (SSNHL). Materials and methods: This retrospective study reviewed records of 106 SSNHL patients categorized into younger (<65 years) and older (≥65 years). Hearing outcomes and related factors including sex, absolute gain, treatment timing, Hyperbaric Oxygen Therapy (HBOT), audiogram type, and contralateral ear thresholds were examined. Results: Treatment outcomes between age groups showed no statistically significant difference (p = 0.053), though younger age was consistently linked to better recovery. A significant negative correlation between age and absolute hearing gain was observed (r = -0.296, p < 0.05). Younger females showed superior outcomes compared to younger males (p < 0.05). Early treatment predicted better recovery (χ² = 9.04, p < 0.01). A normal contralateral ear threshold was associated with better recovery (p < 0.05). A multivariate logistic regression model was developed (AUC = 0.781). Symptom duration (p < 0.05) and intratympanic therapy (p < 0.05) were significant predictors of hearing outcomes. Age was not a significant independent predictor (p = 0.054), but it improved model fit, supporting its clinical relevance. Conclusions: The timing of treatment initiation is important for SSNHL prognosis. Although age did not reach statistical significance in the multivariate model, its consistent association with better outcomes and contribution to model fit highlight its continued clinical relevance. Early intervention is the key predictor of recovery, reinforcing the value of age-informed, personalized treatment strategies in managing SSNHL

    Clinical approach to a child with serious airway obstruction : graduation thesis

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    Children are not simply small adults; rather, they are continuously growing and developing individuals who undergo significant changes each day. As they grow and develop, they explore their environment using all their senses, particularly their mouths. This behavior increases the risk of foreign body ingestion, which may lead to airway obstructions. Respiratory distress can result from obstruction of the upper airway due to larger objects and lower airway obstructions due to smaller ones. However, not all airway obstructions are caused by foreign bodies. Congenital conditions and unique anatomical characteristics, such as a proportionally larger tongue in a smaller oropharynx, may also lead to obstruction. Allergic reactions, including anaphylactic shock, can further result in respiratory distress and cyanosis. In cases of airway obstruction, healthcare professionals follow a structured approach that includes imaging techniques such as ultrasound, X-ray, or MRI. Bronchoscopy is a procedure used for both diagnosis and treatment. Medications like corticosteroids and antihistamines are administered for allergic reactions, while salbutamol is used in asthma cases. In more severe or life-threatening situations, intubation or surgery may be necessary to secure the airway and prevent suffocation

    Lymphoceles in kidney transplant patients

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    Kronična bubrežna bolest je rastući javnozdravstveni problem zbog porasta incidencije, progresivne prirode i ozbiljnih komplikacija. Najčešći uzroci su šećerna bolest tip 2, arterijska hipertenzija i glomerulonefritis. Bolest je često neprepoznata do uznapredovalih stadija, kada je potrebno nadomjesno liječenje dijalizom ili transplantacijom bubrega. Transplantacija je najučinkovitiji način nadomjesnog liječenja. Znatno poboljšava kvalitetu života bolesnika i dugoročno preživljenje, ali nosi rizik od kirurških komplikacija. Jedna od čestih komplikacija transplantacije su limfocele, sa potencijalno ozbiljnim posljedicama. Limfocele nastaju nakupljanjem limfne tekućine zbog oštećenja limfnih puteva tijekom operacije i mogu narušiti funkciju presatka kompresijom uretera i okolnih struktura. Većina limfocela je asimptomatska i slučajan su nalaz na redovnim kontrolama te ne zahtijevaju intervencije, dok je simptomatske limfocele potrebno liječiti. Dijagnosticira se sa ultrazvukom zajedno sa aspiracijom sadržaja radi potvrde i razlikovanja od urinoma. Početno, manje invazivno liječenje uključuje aspiraciju, perkutanu drenažu zajedno sa primjenom sklerozantnih sredstava, ali ima veću stopu recidiva. Invazivne i minimalno invazivne metode su otvorena i laparoskopska marsupijalizacija, te laparoskopska fenestracija limfocele.Chronic kidney disease is a growing public health problem due to its increasing incidence, progressive nature and serious complications. The most common causes are type 2 diabetes, arterial hypertension and glomerulonephritis. The disease is often unrecognized until advanced stages, when replacement treatment with dialysis or kidney transplantation is necessary. Transplantation is the most effective method of replacement treatment. It significantly improves the patient's quality of life and long-term survival, but carries a risk of surgical complications. One of the common complications of transplantation is lymphocele, with potentially serious consequences. Lymphoceles are formed by the accumulation of lymphatic fluid due to damage to the lymphatic vessels during surgery and can impair the function of the graft by compressing the ureter and surrounding structures. Most lymphoceles are asymptomatic and are incidental findings during regular check-ups and do not require intervention, while symptomatic lymphoceles need to be treated. It is diagnosed with ultrasound together with aspiration of the contents to confirm and differentiate from urinoma. Initial, less invasive treatment includes aspiration, percutaneous drainage along with the use of sclerosing agents, but has a higher recurrence rate. Invasive and minimally invasive methods include open and laparoscopic marsupialization, and laparoscopic fenestration of lymphocele

    Sacral neuromodulation

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    Sakralna neuromodulacija predstavlja modernu, minimalno invazivnu terapijsku metodu za liječenje funkcionalnih poremećaja mokraćnog i probavnog sustava, a pogotovo u bolesnika koji imaju slab terapijski odgovor na standardne oblike liječenja. Ova metoda funkcionira tako da se električnom stimulacijom sakralnih živaca, osobito korijene živaca S3, modulira neuralna komunikacija između leđne moždine i zdjeličnih organa. Iako točan mehanizam djelovanja još uvijek nije u potpunosti jasan, brojna istraživanja govore da ova metoda ima pozitivan učinak na motorni i senzorni odgovor zdjeličnih organa. Indikacije za ovu vrstu terapije jesu prekomjerno aktivan mokraćni mjehur, retencija urina bez mehaničkog uzroka, fekalna inkontinencija te kronični bolovi u zdjelici. Unatoč dokazanim kliničkim prednostima, primjena SNM u kliničkoj praksi je i dalje ograničena zbog visoke cijene samog zahvata, potrebe za dugoročnim praćenjem bolesnika nakon zahvata i varijabilnoj dostupnosti ove metode u zdravstvenim sustavima različitih zemalja. Upravo zato što mehanizam djelovanja nije potpuno poznat također utječe na ograničenu upotrebu ove metode. Potrebna su dodatna istraživanja kako bi se poboljšala selekcija bolesnika odnosno definirale indikacije, smanjili troškovi te omogućila veća dostupnost ove terapijske metode koja potencijalno mijenja i poboljšava kvalitetu života bolesnika.Sacral neuromodulation is a modern, minimally invasive therapeutic method for the treatment of functional disorders of the urinary and digestive systems, especially in patients who have a poor therapeutic response to standard forms of treatment. This method works by modulating neural communication between the spinal cord and pelvic organs by electrical stimulation of the sacral nerves, especially the S3 nerve roots. Although the exact mechanism of action is still not completely clear, numerous studies show that this method has a positive effect on the motor and sensory response of the pelvic organs. Indications for this type of therapy are overactive bladder, urinary retention without a mechanical cause, fecal incontinence and chronic pelvic pain. Despite proven clinical advantages, the application of SNM in clinical practice is still limited due to the high cost of the procedure itself, the need for long-term follow-up of patients after the procedure and the variable availability of this method in the healthcare systems of different countries. The fact that the mechanism of action is not fully understood also affects the limited use of this method. Additional research is needed in order to improve the selection of patients, i.e. to define the indications, reduce costs and enable greater availability of this therapeutic method, which potentially changes and improves the quality of life of patients

    Oxidative stress in cardiac surgery

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    Oksidacijski stres tijekom i nakon kirurških zahvata predstavlja značajan patofiziološki izazov jer može dovesti do oštećenja stanica, pokretanja upalnog odgovora i razvoja brojnih poslijeperacijskih komplikacija. Tijekom operacija, osobito pri korištenju CPB-a, dolazi do povećanog stvaranja ROS-a koji premašuje kapacitet antioksidacijskih obrambenih mehanizama organizma. Glavni izvori ROS-a su ishemijsko-reperfuzijska ozljeda, mehaničko oštećenje tkiva, kontakt krvi s umjetnim površinama i promjene tjelesne temperature tijekom operacije. Oksidacijski stres pridonosi upalnim procesima i oštećenju ključnih biomolekula poput lipida, proteina i DNA, što dovodi do disfunkcije miokarda, aritmija, akutnog oštećenja bubrega i neurokognitivnih komplikacija. Smanjenje oksidacijskog stresa ključno je za očuvanje funkcije organa i poboljšanje poslijeoperacijskog ishoda. Terapijski pristupi uključuju farmakološke metode, poput primjene antioksidacijskih vitamina C i E, trimetazidina, NAC-a i statina, koji pomažu u neutralizaciji ROS-a i očuvanju mitohondrijske funkcije. Nefarmakološke strategije, uključujući optimizaciju tjelesne temperature, korištenje biokompatibilnih materijala u CPB sustavu, prilagodbu perfuzije i primjenu tehnika ishemijskog prekondicioniranja i postkondicioniranja, dodatno doprinose zaštiti tkiva. Naglašena je važnost individualiziranog pristupa pacijentu, prepoznavanju rizika i implementacije kombiniranih terapijskih strategija kako bi se smanjila učestalost komplikacija i poboljšao klinički ishodOxidative stress during and after cardiac surgery represents a significant pathophysiological challenge, contributing to cellular damage, triggering inflammatory responses, and leading to various postoperative complications. During cardiac surgery, particularly when using CPB, the production of reactive oxygen species increases beyond the capacity of the body’s antioxidant defense systems. Major sources of ROS include ischemia-reperfusion injury, mechanical tissue damage, contact between blood and artificial surfaces, and fluctuations in body temperature during surgery. Oxidative stress promotes inflammatory processes and damages key biomolecules such as lipids, proteins, and DNA, resulting in myocardial dysfunction, arrhythmias, acute kidney injury, respiratory disorders, and neurocognitive complications. Reducing oxidative stress is crucial for preserving organ function and improving postoperative outcomes. Therapeutic approaches involve pharmacological methods, such as the use of antioxidant vitamins C and E, trimetazidine, N-acetylcysteine, and statins, which help neutralize ROS and protect mitochondrial function. Non-pharmacological strategies, including temperature control, use of biocompatible materials in CPB systems, perfusion optimization, and ischemic pre-conditioning and post-conditioning techniques, further contribute to tissue protection. The importance of an individualized approach to patient care, risk identification, and the implementation of combined therapeutic strategies to reduce complication rates and enhance clinical outcomes has been emphasized

    Zeolite 5 A mediated palmitic acid detection in tomato seed oil by photoionization detector

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    Tomato seed oil (TSO) is an edible product characterized by a wide range of molecules, with beneficial effects on human health. Volatile organic compounds (VOC) formed from the degradation of fatty acids, are promising candidates for the characterization of vegetable oils. Hereafter, a sensor based on photoionization detector for palmitic acid is presented. The sensor exploits thermal emission profile analysis from a thin layer of zeolite 5 A. Emissive profiles were acquired through a Photoionization Detector (PID) at 100 degrees C. Specifically, the combination of use of zeolite with pore size of 5.1 & Aring; and an ultraviolet lamp of 10.9 eV allows selective adsorption and detection of palmitic acid in a solution of pentane and TSO. The PID-zeolite sensor was investigated using oils at different dilution and at different storage conditions (-20 degrees C, 4 degrees C and 25 degrees C). Results evidenced that pentane dilution plays a significant role in palmitic acid adsorption, with a maximum emissive profile at similar to 885 mu mol/L. Low temperature storage (-20 degrees C) of samples before analysis results in 1.5 times higher emission peak due to the formation of triple chain molecular arrangement of palmitic acid. Calibration evidenced a linear range from 0.45 mmol/L up to 1.8 mmol/L with a sensitivity of 34.65 ppm center dot mmol(-1)center dot L and an R-2 = 0.92. Real scenario analysis was performed a mixture of TSO with soybean oil (SO) at different storage stability. A significant emissive reduction in palmitic acid was observed in mixed oil, depending on its stability which allows for the evaluation of adulterated samples

    Intrakapsularni temporomandibularni poremećaji označavaju aktivnost aksijalnog spondiloartritisa

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    Objectives: The group of spondyloarthritis (SpA) disorders shares common clinical manifestations, including internal derangement (ID) of temporomandibular joint (TMJ). This study aimed to investigate SpA activity in patients with ID of TMJ. Materials and Methods: We assessed 200 patients with neck pain using the Assessment of Spondyloarthritis International Society (ASAS) criteria. TMJ was examined using Diagnostic Criteria for Temporomandibular Disorders (DC/TMD protocol). Patients with SpA were divided into three groups: symptomatic ID of TMJ, asymptomatic ID of TMJ, or healthy TMJ (controls). Activity of SpA was evaluated using the Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Disease Activity Index in Psoriatic Arthritis (DAPSA), patients’ self-estimated SpA activity, difficulties in performing daily activities, pain intensity (visual analogue scale) and laboratory parameters. Results: Patients with symptomatic and asymptomatic ID showed statistically significantly increased ASDAS, anti-streptolysin titer, patients’ self-estimated axial pain and activity of SpA, and decreased hematocrit than the control. Patients with symptomatic ID also had statistically significant earlier onset of SpA, along with increased BASDAI and DAPSA, total body pain, difficulties in performing daily activities, platelet count, and serum alpha-amylase but lower hemoglobin concentration than controls. Patients with asymptomatic ID had higher frequencies of exacerbated axial SpA and sacroiliac joint ankylosis compared to the control. Conclusion: All patients with SpA and ID showed increased axial disease activity.Cilj rada: Skupina bolesti spondiloartritisa (SpA) ima zajedničke kliničke pojavnosti, uključujući intrakapsularni temporomandibularni poremećaj (IK TMP). Ovo istraživanje imalo je za cilj istražiti aktivnost SpA-e kod bolesnika s IK TMP-om. Materijali i metode: Dijagnosticirali smo SpA kod 200 bolesnika s bolovima u vratu koristeći se međunarodnom razradbom ASAS (engl. The Assessment of SpondyloArthritis International Society). Temporomandibularni zglob (TMZ) pregledan je s pomoću protokola Dijagnostički kriteriji za temporomandibularne poremećaje (DK/TMP). Bolesnici sa SpA-om podijeljeni su u tri skupine: simptomatski IK TMP, asimptomatski IK TMP ili zdravi TMZ (kontrola). Aktivnost SpA-e procijenjena je korištenjem ASDAS-a (engl. Ankylosing Spondylitis Disease Activity Score), BASDAI-ija (engl. Bath Ankylosing Spondylitis Disease Activity Index), DAPSA-e (engl. Disease Activity Index in Psoriatic Arthritis), aktivnosti SpA-e koju su bolesnici sami procijenili, poteškoća u obavljanju dnevnih aktivnosti, jakosti bolova (vizualna analogna ljestvica) i laboratorijskim parametrima. Rezultati: Bolesnici sa simptomatskim i asimptomatskim IK TMP-om imali su statistički značajno veći ASDAS, titar antistreptolizina, samoprocjenu aksijalne boli i aktivnost SpA-e te smanjeni hematokrit u odnosu prema kontroli. Bolesnici sa simptomatskim IKTMP-om dodatno su imali statistički značajno raniji početak SpA-e, zajedno s povećanim BASDAI-jem i DAPSA-om, bolovima u cijelom tijelu, poteškoćama u obavljanju dnevnih aktivnosti, broju trombocita i koncentracijom α-amilaze u serumu, ali manju koncentraciju hemoglobina od kontrole. Bolesnici s asimptomatskim IK TMP-om imali su veću učestalost pogoršanja aksijalnoga spondiloartritisa (SpA) i ankiloze sakroilijačnoga zgloba u usporedbi s kontrolom. Zaključak: Kod svih bolesnila sa SpA-om i IK TMP-om zabilježena je povećana aksijalna aktivnost bolesti

    ADAR1 p150 prevents HSV-1 from triggering PKR/eIF2α-mediated translational arrest and is required for efficient viral replication

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    Adenosine deaminase acting on dsRNA 1 (ADAR1) catalyzes the deamination of adenosines to inosines in double-stranded RNAs (dsRNA) and regulates innate immunity by preventing the hyperactivation of cytosolic dsRNA sensors such as MDA5, PKR or ZBP1. ADAR1 has been shown to exert pro- and antiviral, editing-dependent and editing-independent functions in viral infections, but little is known about its function in herpesvirus replication. We now demonstrate that herpes simplex virus 1 (HSV-1) hyperactivates PKR in the absence of ADAR1, resulting in eIF2α mediated translational arrest and reduced viral replication. Silencing of PKR or inhibition of its downstream effectors by viral (ICP34.5) or pharmacological (ISRIB) inhibitors rescues viral replication in ADAR1-deficient cells. Upon infection, ADAR1 p150 interacts with PKR and prevents its hyperactivation. Our findings demonstrate that ADAR1 is an important proviral factor that raises the activation threshold for sensors of innate immunity

    Funkcionalni poremećaji pokreta i fizioterapija

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    Uvod: Funkcionalni poremećaji pokreta onesposobljavajuće su neuropsihijatrijsko stanje koje predstavlja dijagnostički i terapijski izazov. U zbrinjavanju osoba s funkcionalnim poremećajem pokreta bitan je multidisciplinarni pristup, a fizioterapija se pokazala kao jedna od ključnih komponenti. Cilj: Istražiti utjecaj fizioterapije kod funkcionalnih poremećaja pokreta Materijali i metode: Literatura je pretraživana u elektronskim bazama podataka Medline i PubMed, a korištene su ključne riječi: functional movement disorder, psychogenic movement disorder, physical therapy, multidisciplinary team. Rezultati: Nakon pretraživanja i filtriranja radova sukladno navedenom cilju u obzir je uzeto 10 radova koji daju relevantne i detaljne podatke te tematikom odgovaraju cilju istraživanja. Zaključak: Uloga fizioterapeuta neophodna je u fizioterapijskoj procjeni i provođenju fizioterapijskih postupak kod pacijenata s funkcionalnim poremećajima pokreta. Fizioterapija doprinosi smanjena simptoma i poboljšanja kvalitete života kod osoba s funkcionalnim poremećajem pokreta

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