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Öğe Different cortex activation between young and middle-aged people during different type problem-solving: an EEG&fNIRS study(2025) Sarıcaoğlu, Mevhibe; Yücel, Meryem Ayşe; Budak, Miray; Omurtag, Ahmet; Hanoğlu, LütfüProblem-solving strategies vary depending on the type of problem and aging. This study investigated the hemodynamic response measured by the changes in the oxyhemoglobin concentration (HbO), alpha frequency power, and their interrelation during problem-solving in healthy young and middle-aged individuals, employing combined electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) recordings. The study included 39 young and 30 middle-aged subjects. The brain activation that occurred while answering different questions was recorded using combined EEG and fNIRS. During the EEG & fNIRS recording, four questions (arithmetic, general knowledge, insight, and basic operation) were used for problem-solving. Alpha power (8–13 Hz) and HbO changes were analyzed. The behavioral results indicated significant differences between age groups in various question types. While the middle-aged group performed better on the general knowledge questions, the older group performed better on the insight and four-process questions. The fNIRS results reveal significant differences in brain activation during problem-solving tasks, particularly in regions like DLPFC/TA, STG, pSSC/Wernicke, and STG/angular gyrus Wernicke's area. The young group with the highest HbO was recorded during arithmetic questions, general knowledge questions, and basic operation questions. In contrast, there was no significant highest HbO during insight questions. Similar findings were observed in the middle-aged group, with the highest HbO recorded during general knowledge questions. However, there was no significant HbO in other channels during the solving of other question types in this group. The alpha power varied across different electrodes for various question types in both young and middle-aged groups. The highest alpha frequency band power for different electrodes was recorded while solving general knowledge questions in the young group and insight questions in the middle-aged group. Finally, the EEG and fNIRS correlation results showed positive correlations between HbO and alpha frequency band power in specific brain regions while solving general knowledge questions, particularly in the middle-aged group. The study reveals age-related differences in behavioral performance, brain activation patterns, and neural correlates during various cognitive tasks, showcasing distinct strengths between middle-aged and young individuals in specific question types.Öğe Frontocentral delta and theta oscillatory responses are sensitive to sleep deprivation during a working memory task(2025) Yırıkoğulları, Harun; Dalmızrak, Esra; Güntekin, BaharSleep deprivation has become a severe public health problem in modern societies. Negative consequences of prolonged wakefulness on cognitive abilities have been demonstrated and working memory is one of the main cognitive functions that can be affected by sleep deprivation. This study aims to investigate the effects of sleep deprivation on working memory through EEG event-related oscillations. Thirty healthy young adult university students and graduates were included in this study (15 rested control – 15 sleep-deprived). A 2-back task was used to evaluate working memory, and both groups performed the task during EEG recording. The sleep-deprived (SD) group was required to stay awake for 24 h, and then the EEG session was conducted. The rested control (RC) subjects participated in the morning after a regular night's sleep. Event-related power and phase-locking analyses were applied, and delta (1–3.5 Hz), theta (4–6.5 Hz) and alpha (8–13 Hz) frequencies were investigated in the time-frequency domain. In the 2-back task, significantly prolonged reaction times were observed in the SD group. However, the decrease in accuracy rate was not significant. The EEG analyses revealed that the SD group had decreased frontocentral event-related delta and theta power responses after the presentation of stimuli. Moreover, task accuracy was positively correlated with the left frontocentral delta power in the SD group, and theta power in the RCs. Thus, we propose that the adverse effects of sleep deprivation on working memory can be observed through low-frequency oscillatory responses in the brain.Öğe Multi-omics characterization of improved cognitive functions in parkinson's disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial(2025) Yuluğ, Burak; Altay, Özlem; Hanoğlu, Lütfü; Velioğlu, Halil Aziz; Coşkun, Ebru; Bayraktaroğlu, Zübeyir; Mardinoğlu, AdilParkinson’s disease is primarily marked by mitochondrial dysfunction and metabolic abnormalities. We recently reported that the combined metabolic activators improved the immunohistochemical parameters and behavioural functions in Parkinson’s disease and Alzheimer’s disease animal models and the cognitive functions in Alzheimer’s disease patients. These metabolic activators serve as the precursors of nicotinamide adenine dinucleotide and glutathione, and they can be used to activate mitochondrial metabolism and eventually treat mitochondrial dysfunction. Here, we designed a randomized, double-blinded, placebo-controlled phase II study in Parkinson’s disease patients with 84 days combined metabolic activator administration. A single dose of combined metabolic activator contains L-serine (12.35 g), N-acetyl-L-cysteine (2.55 g), nicotinamide riboside (1 g) and L-carnitine tartrate (3.73 g). Patients were administered either one dose of combined metabolic activator or a placebo daily for the initial 28 days, followed by twice-daily dosing for the next 56 days. The main goal of the study was to evaluate the clinical impact on motor functions using the Unified Parkinson’s Disease Rating Scale and to determine the safety and tolerability of combined metabolic activator. A secondary objective was to assess cognitive functions utilizing the Montreal Cognitive Assessment and to analyse brain activity through functional MRI. We also performed comprehensive plasma metabolomics and proteomics analysis for detailed characterization of Parkinson’s disease patients who participated in the study. Although no improvement in motor functions was observed, cognitive function was shown to be significantly improved (P < 0.0000) in Parkinson’s disease patients treated with the combined metabolic activator group over 84 days, whereas no such improvement was noted in the placebo group (P > 0.05). Moreover, a significant reduction (P = 0.001) in Montreal Cognitive Assessment scores was observed in the combined metabolic activator group, with no decline (P > 0.05) in the placebo group among severe Parkinson’s disease patients with lower baseline Montreal Cognitive Assessment scores. We showed that improvement in cognition was associated with critical brain network alterations based on functional MRI analysis, especially relevant to areas with cognitive functions in the brain. Finally, through a comprehensive multi-omics analysis, we elucidated the molecular mechanisms underlying cognitive improvements observed in Parkinson’s disease patients. Our results show that combined metabolic activator administration leads to enhanced cognitive function and improved metabolic health in Parkinson’s disease patients as recently shown in Alzheimer’s disease patients.Öğe Resting-state electroencephalographic rhythms depend on sex in patients with dementia due to parkinson's and lewy body diseases an exploratory study(2025) Del Percio, Claudio; Lizio, Roberta; Lopez, Susanna; Güntekin, Bahar; Hanoğlu, Lütfü; Helvacı Yılmaz, Nesrin; Babiloni, ClaudioParkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are more prevalent in males than females. Furthermore, they typically showed abnormally high delta (< 4 Hz) and low alpha (8–10 Hz) rhythms from resting-state electroencephalographic (rsEEG) activity. Here, we hypothesized that those abnormalities may depend on the patient's sex. An international database provided clinical-demographic-rsEEG datasets for cognitively unimpaired older (Healthy; N = 49; 24 females), PDD (N = 39; 13 females), and DLB (N = 38; 15 females) participants. Each group was stratified into matched female and male subgroups. The rsEEG rhythms were investigated across the individual rsEEG delta, theta, and alpha frequency bands based on the individual alpha frequency peak. The eLORETA freeware was used to estimate cortical rsEEG sources. In the Healthy group, widespread rsEEG alpha source activities were greater in the females than in the males. In the PDD group, widespread rsEEG delta source activities were lower and widespread rsEEG alpha source activities were greater in the females than in the males. In the DLB group, central-parietal rsEEG delta source activities were lower, and posterior rsEEG alpha source activities were greater in the females than in the males. These results suggest sex-dependent hormonal modulation of neuroprotective-compensatory neurophysiological mechanisms in PDD and DLB patients underlying the generation of rsEEG delta and alpha rhythms, which should be considered in the treatment of vigilance dysregulation in those patients.Öğe Computational study of the activation mechanism of wild-type parkin and its clinically relevant mutant(2025) Cinviz, Zeynep Nur; Şensoy, ÖzgeParkinson's disease (PD) is the second most prevalent neurodegenerative disorder. It impairs the control of movement and balance. Parkin mutations worsen the symptoms in sporadic cases and cause the early onset of the disease. Therefore, recent efforts have focused on the rescue of defective parkin by engineered proteins or small-molecule activators to enhance parkin activation. These attempts require holistic understanding of the multistep activation mechanism and molecular effects of disease-associated mutations. Hereby, we provided a comprehensive analysis of the activation mechanism of parkin and a clinically relevant mutant, parkinS167N, using molecular dynamics simulations based on the following crystal structures: (1) parkin, (2) parkin/pUb (phosphorylated Ubiquitin), (3) pparkin/pUb, and (4) pparkin/pUb/UbcH7-Ub. Each of these represents an individual step in the activation process. We showed that the mutation impacted the dynamics of not only the RING0 domain, where it is localized, but also the RING2, Ubl, and IBR domains. We identified residues participating in the allosteric interaction network involved in parkin activation. Some of them are mutated in PD-associated parkin variants. The RING0 domain provides a binding interface with various proteins, so understanding problems associated with the mutation paves the way to the discovery of effective engineered proteins or small molecules that activate mutant parkin.Öğe Biosynthesis of zinc oxide nanoparticles using dried leaves of camellia sinensis: methods to characterize and assess their effects on mesenchymal stem cell viability(2025) Yeşilkır Baydar, Serap; Akgül Çağlar, Tuba; Koç, Fatma EbruStem cell nanotechnology (SCN) is an important scientific field to guide stem cell-based research of nanoparticles. Currently, nanoparticles (NPs) have a rich spectrum regarding the sources from which they are obtained (metallic, polymeric, etc.), the methods of obtaining them (physical, chemical, biological), and their shape, size, electrical charge, etc. properties. It is also essential to expand green synthesis applications for the use of NPs in the field of biomedical sciences. For this purpose, there is a need to produce NPs using biological sources (plant, microorganism, algae, yeast etc.…), characterization and investigation of their effects on biological activities of stem cells. This process involves long and laborious procedures, and there may be differences in methods between individual laboratories.In this protocol, biofabrication and characterization of ZnO NPs using dried leaves of Camellia sinensis is described. This experimental setup includes conventional and novel methods that can be applied to biofabricate and characterize the NPs and to examine the viability, apoptotic, and necrotic effects on human adipose tissue-derived mesenchymal stem cells (ADMSCs) in vitro.Öğe Dose-dependent effect of a new biotin compound in hippocampal remyelination in rats(2025) Yuluğ, Burak; Kılıç, Ertuğrul; Oğuz, Tuba; Orhan, Cemal; Er, Beşir; Tuzcu, Mehmet; Şahin, KazımDemyelination is commonly observed in neurodegenerative disorders, including multiple sclerosis (MS). Biotin supplementation is known to stabilize MS progression. To reduce the effective dose of biotin, we synthesized a new and superior form of biotin, a complex of magnesium ionically bound to biotin (MgB) and compared its dose-dependent effect with biotin alone after inducing demyelination using lysolecithin (LPC) in rats. Myelination was assessed using luxol fast blue staining and immunostaining against MBP protein, revealing that the most significant remyelination occurred in the MgB groups. Additionally, both biotin and MgB-treated animals showed dose-dependent improvements in spatial memory. Moreover, we detected a decrease in inflammatory proteins in both treatment groups, which was more prominent in high-dose MgB-treated animals and correlated with decreased expression of NF-kappa B p65, OP, and MMP-9 proteins. Further analysis of biotin-related proteins demonstrated that both biotin and, notably, MgB reversed the demyelination-dependent reduction of these proteins. Furthermore, biotin, particularly MgB, improved neuronal transmission proteins, Synapsin-1, PSD-93, and PSD-95. Additionally, both treatment groups exhibited increased BDNF, GAP43, and ICAM levels, with significant increments observed in high-dose MgB-treated animals. Increased GFAP, indicative of reactive gliosis, was observed in LPC-treated animals, and this effect was notably reversed by high-dose MgB treatment. The current data emphasize the dose-dependent beneficial effect on the remyelination process. Furthermore, the combination of biotin with Mg resulted in a more potent effect compared to biotin by itself. The strong influence of MgB encourages proof-of-concept studies using MgB in patients with MS.Öğe Association of nox5 expression with sperm activity and motility in pathospermic infertile men(2024) Daylan, Benay; Tok, Olgu Enis; Çakıcı, Çağrı; Yiğitbaşı, Türkan; Varlı Yelke, Tuba; Şenel Ustabaş, Tuğba; Ayla, ŞuleBackground: The newest NOX isoform, NOX5, has been found in mammalian spermatozoa. Many physiological and pathological situations in spermatozoa are mediated by reactive oxygen species (ROS). NOX5 is the main source of ROS in spermatozoa. Our purpose was to investigate the changes in NOX5 expression and the effect of NOX5 expression on sperm motility, chromatin integrity, and oxidative status in oligoasthenozoospermic compared to normozoospermic men. Methods: Semen samples were collected from 30 normozoospermic (NS) and 30 oligoasthenozoospermic (OAS) men. NOX5 protein expression in sperm samples was evaluated by immunohistochemistry and western blot. Oxidative stress status was evaluated by total antioxidant capacity (TAC), total oxidant capacity (TOC), and oxidative stress index (OSI) parameters. Chromatin integrity in spermatozoa was evaluated by toluidine blue staining. Results: NOX5 expression levels were significantly higher in OAS group than in NS group (p<0.001). In addition, chromatin integrity was significantly higher in the OAS group in comparison to NS group (p<0.001). TAC levels were higher in the NS group, but OSI and TOC levels were significantly higher in OAS group (p<0.001). It was found that NOX5 protein expression was positively correlated with oxidative stress and chromatin integrity and negatively correlated with motility (p<0.01). Conclusion: These results suggest that overexpression of NOX5 may be the source of excessive ROS production and oxidative stress injuries in oligoasthenozoospermic men. Considering that NOX5 expression is positively correlated with oxidative stress and chromatin integrity but negatively correlated with motility, it can be considered a biomarker to be used in assisted reproductive procedures.Öğe Glow in the dark tumor: enhanced near-ir visualization and destruction of cancer with a self-quenched theranostic(2025) Güler, Selen İrem; Altan, Cem Levent; Demircioğlu, Emine Esma; Verimli, Nihan; Abisoğlu, Beyza; Bayraktaroğlu, Çiğdem; Erdem, Sultan SibelLate diagnosis is one of the major obstacles for the treatment of breast cancer which can be overcome with a system offering sensitive imaging and selective therapeutic effect. In this study, we developed a “dark-bright” multifunctional drug delivery system bringing real-time imaging and non-invasive therapy together. Theranostic ability of the system was delivered by Verteporfin (VP), serving as a fluorescence probe and a photosensitizer. To create a “dark state” system via self-quenching ability of VP, it was immobilized onto the superparamagnetic iron oxide nanoparticle (SPION) surface. Upon cellular uptake of the “dark state” system, release of VP led to fluorescence regain, switching the system to “bright state” after which photodynamic therapy (PDT) was initiated to lead to cell death. Theranostic feature of the system was evaluated in MCF-7 and MDA-MB-231 cell lines. Following internalization, fluorescence signal was increased up to ∼56-fold in MCF-7 cells. The IC50 value decreased ∼20-fold and ∼117-fold in MCF-7 and MDA-MB-231 cell lines, respectively. Moreover, the system significantly inhibited migration in the highly aggressive MDA-MB-231 cell line and induced apoptosis by caspase-3 activation. The developed “dark-bright” system is a promising multifunctional drug delivery vehicle with extraordinary theranostic features for the detection and destruction of micro tumors.Öğe Anticancer properties of phenylboronic acid in androgen-dependent (lncap) and androgen-independent (pc3) prostate cancer cells via map kinases by 2d and 3d culture methods(2025) Gürsoy Gürgen, Duygu; Güneş, Arzu; Köse, Oğuzhan; Kaplan, Arife Ahsen; Karabulut, Seda; Tunalı, Muzaffer Başak; Keskin, İlknurObjective: This study utilized three cell lines: normal prostate epithelial RWPE-1, androgen-dependent LNCaP, and androgen-independent PC3. We investigated the inhibitory effects of phenylboronic acid (PBA)’s inhibitory effect on cellular proliferation due to its ability to disrupt microtubule formation in prostate cancer cell lines. Additionally, this study aimed to assess the cytotoxic effects of PBA on prostate cancer cells using two-dimensional (2D) and three-dimensional (3D) cell culture models. Methods: The IC50 values of PBA and colchicine were determined through viability assays in 2D and 3D models. Colony formation, proliferation, and migration assays were conducted. Immunofluorescence intensity analysis of MAPKKK proteins (ERK, JNK, p38) was performed to explore the mechanism of cellular response to PBA. Results: The IC50 values were determined for each treatment group. After 48-hour of PBA treatment, migration was inhibited more effectively than with colchicine in both cancer cell lines. After 24-hour, PBA reduced colony formation and proliferation. PBA treatment for 24-hour decreased JNK expression in PC3 and LNCaP cells in 2D models. Both PBA and colchicine increased p38 expression in PC3 spheroids. PBA’s effects on cell deformation were visualized in semi-thin sections, marking the first ultrastructural observation of PBA-induced morphological defects in cancer cells. Conclusion: PBA exerts antimitotic effects by inhibiting proliferation and migration and triggers diverse metabolic responses across different cell lines. Furthermore, PBA’s low toxicity on RWPE-1 cells suggests its potential as a promising chemotherapeutic agent for future studies.Öğe Boosting the electrochemical performance of ternary metal oxide anode in lithium-ion batteries via biomass-derived carbon nanodot modification(2025) Karahan, Billur Deniz; Gülcan, Mehmet FeryatTransition metal oxides deliver high capacity but demonstrate a short cycle life when they are utilized as the anode active material in lithium ion batteries. This study offers an innovative solution to this problem by designing new composite materials in which, the modification of ternary transition metal oxide by carbon nanodots is utilized. Carbon nanodots isolated from Phoenix Dactylifera L. seeds are used by the authors for the first time to process hydrothermally produced zinc nickel ferrite powders. Subsequently, the combination is treated in a rotating evaporator to provide a uniform mix. Then, the finished product is heated to 600 °C in air. Once these powders (ternary metal oxide from hydrothermal (Sample 1) and C-dot modified ternary metal oxide (Sample 2)) are utilized as anode active materials, Sample 2 performs 1224.74 mAh g−1 at the 200th cycles upon the application of 0.1 mA g−1 current load in cycling. Sample 2 tested under various current loads ranging from 0.1 to 2 A g−1 it delivers 1229.08 mAh g−1 at the 270th cycle. It is thus demonstrated that through careful material selection and process design it is possible to synthesize sustainable anode active materials that could withstand high current loads, with long cycle life. It is anticipated that the encouraging outcomes of this study would open up new vistas to design sustainable composite anode active materials.Öğe Distinctive delta and theta responses in deductive and probabilistic reasoning(2025) Sevim, Emir Faruk; Yıldırım, Yasin; Ünsal, Esra; Dalmızrak, Esra; Güntekin, BaharIntroduction: The neural substrates of reasoning, a cognitive ability we use constantly in daily life, are still unclear. Reasoning can be divided into two types according to how the inference process works and the certainty of the conclusions. In deductive reasoning, certain conclusions are drawn from premises by applying the rules of logic. On the other hand, in probabilistic reasoning, possible conclusions are drawn by interpreting the semantic content of arguments. Methods: We examined event-related oscillations associated with deductive and probabilistic reasoning. To better represent the natural use of reasoning, we adopted a design that required participants to choose what type of reasoning they would use. Twenty healthy participants judged the truth values of alternative conclusion propositions following two premises while the EEG was being recorded. We then analyzed event-related delta and theta power and phase-locking induced under two different conditions. Results: We found that the reaction time was shorter and the accuracy rate was higher in deductive reasoning than in probabilistic reasoning. High delta and theta power in the temporoparietal, parietal, and occipital regions of the brain were observed in deductive reasoning. As for the probabilistic reasoning, prolonged delta response in the right hemisphere and high frontal theta phase-locking were noted. Conclusion: Our results suggest that the electrophysiological signatures of the two types of reasoning have distinct characteristics. There are significant differences in the delta and theta responses that are associated with deductive and probabilistic reasoning. Although our findings suggest that deductive and probabilistic reasoning have different neural substrates, consistent with most of the studies in the literature, there is not yet enough evidence to make a comprehensive claim on the subject. There is a need to diversify the growing literature on deductive and probabilistic reasoning with different methods and experimental paradigms.Öğe The role of circadian rhythm proteins rev-erbα and β in the development of neuronal injury after traumatic brain injury(2024) Pençe, Mahmud Esad; Doğan, Enes; Koç, Halil İbrahim; Bayraktaroğlu, Çiğdem; Altunay, Serdar; Kılıç, Ertuğrul; Beker, Mustafa ÇağlarBackground/aim: Circadian rhythm proteins (CRPs) play critical roles in both physiological and pathophysiological conditions, including neurodegenerative disorders. As members of CRPs, the nuclear receptors Rev-Erbα/β regulate circadian rhythm particularly by inhibiting Bmal1 protein and are involved in the neuroinflammation and cell death processes. However, their roles in the development of neuronal injury after traumatic brain injury (TBI) were largely unexplored, and so were investigated in the present study. Materials and methods: For the induction of TBI, animals were subjected to the cryogenic model of TBI, which is a commonly used animal model and shares essential similarities with cerebral ischemia in terms of pathophysiological cascades. To assess the impact of Rev-Erb proteins on TBI, both Rev-Erbα and Rev-Erbβ proteins were activated or deactivated, and their expression profiles were determined by western blot analyses. Infarct volume and brain swelling were analyzed by cresyl violet staining. Blood–brain barrier (BBB) permeability was analyzed by immunoglobulin G extravasation. Neuronal survival was analyzed by NeuN immunohistochemistry. Results: Our observations indicate that Rev-Erbβ significantly reduced brain injury after TBI, which was reversed by inhibiting this protein. Not activation but the inhibition of both Rev-Erb proteins increased brain swelling significantly. In addition, both Rev-Erbα and Rev-Erbβ improved BBB permeability and neuronal survival significantly, which were reversed by their inhibitions. Conclusion: Our results show that Rev-Erbα and particularly Rev-Erbβ play significant roles in the development of neuronal injury after TBI. Our findings suggest that Rev-Erb proteins would be a potential therapeutic target for the treatment of neurodegenerative diseases.Öğe Hippocampal connectivity dynamics and volumetric alterations predict cognitive status in migraine: a resting-state fMRI study(2025) Çankaya, Şeyda; Ayyıldız, Behçet; Sayman, Dila; Yalçınkaya, Ali; Hanoğlu, Lütfü; Velioğlu, Halil Aziz; Yuluğ, BurakThe etiology of cognitive decline linked to migraine remains unclear, with a growing recurrence rate and potential increased dementia risk among sufferers. Cognitive dysfunction has recently gained attention as a significant problem among migraine sufferers that can be related to alterations in hippocampal function and structure. This study explores hippocampal subfield connectivity and volume changes in migraine patients. We recruited 90 individuals from Alanya University's Neurology Department, including 49 migraine patients and 41 controls, for functional and anatomical imaging. Using the CONN toolbox and FreeSurfer, we assessed functional connectivity and subfield volumes, respectively. Montreal Cognitive Assessment (MOCA) was used to assess cognition in the entire sample. As a result, migraine patients exhibited significantly lower MOCA scores compared to controls (p<.001). Also, we found significant differences in hippocampal subfields between migraine patients and control groups in terms of functional connectivity after adjusting for years of education; here we showed that the left CA3 showed higher connectivity with right MFG and right occipitolateral cortex. Furthermore, the connectivity of left fimbria with the left temporal lobe and hippocampus and the connectivity of the right hippocampal-tail with right insula, heschl's gyrus, and frontorbital cortex were lower in the migraineurs. Additionally, volumes of specific hippocampal subfields were significantly lower in the migraineurs (whole hippocampus p = 0.004, whole hippocampus head p = 0.003, right CA1 head p = 0.006, and right HATA p = 0.005) compared to controls. In conclusion, these findings indicate that migraine-associated cognitive impairment involves significant functional and structural brain changes, particularly in the hippocampus, which may heighten dementia risk. This pioneering study unveils critical hippocampal alterations linked to cognitive function in migraine sufferers, underscoring the potential for these changes to impact dementia development.Öğe Assessing self-administration of medication: video-based evaluation of patient performance in the ablymed study(2024) Luegering, Anneke; Langner, Robert; Wilm, Stefan; Doeppner, Thorsten Roland; Hermann, Dirk Matthias; Frohnhofen, Helmut; Gronewold, JanineBackground: Older adults often face challenges in medication management due to multimorbidity and complex medication regimens, which frequently go unreported. Unrecognized problems, however, may lead to a loss of drug efficacy and harmful side effects. This study aimed to quantify the prevalence of such problems by applying a novel video-based assessment procedure in a sample of elderly patients. Methods: In this study, 67 elderly in-patients (≥70 years old and regularly taking ≥5 different drugs autonomously) from the ABLYMED study participated in a placebo-based assessment of medication management with five different dosage forms in an instructed manner while being filmed. Patient performance was quantified by the median value of two raters who evaluated each step of medication administration, which were summed to sum scores for each dosage form and an overall impression for each dosage form with a standardized and previously validated rating scheme. Results: The median (Q1;Q3) sum score for tablets was 7.0 (5.0;8.0) with a theoretical range between 4.0 and 17.0, for eye-drops 2.0 (1.0;2.0) with a theoretical range between 1.0 and 5.0, for oral drops 4.0 (3.0;6.0) with a theoretical range between 3.0 and 12.0, for pens 7.0 (5.0;9.0) with a theoretical range between 4.0 and 17.0 and for patches 5.0 (4.0;7.0) with a theoretical range between 3.0 and 15.0. The most difficult step of medication administration was peeling off the protective liner of a patch: 30% had severe difficulties or it was not possible, 21% had moderate difficulties and 49% had mild or no difficulties. Discussion: In a sample of patients with autonomous medication management, our novel assessment procedure identified a substantial fraction of patients with handling problems for each dosage form. This suggests that patients´ medication management problems should be assessed regularly in clinical routine and tackled by patient-individual training or modification of the prescribed drug regimens to achieve effective drug therapy in the elderly.Öğe Temporal microbiome changes in axolotl limb regeneration: stage-specific restructuring of bacterial and fungal communities with a flavobacterium bloom during blastema proliferation(2024) Altın, Hanne; Delice, Büşra; Yıldırım, Berna; Demircan, Turan; Yıldırım, SüleymanThe intricate relationship between regeneration and microbiota has recently gained attention, spanning diverse model organisms. Axolotl (Ambystoma mexicanum) is a critically endangered salamander species and a model organism for regenerative and developmental biology. Despite its significance, a noticeable gap exists in understanding the interplay between axolotl regeneration and its microbiome. Here, we analyse in depth bacterial 16S rRNA amplicon dataset that we reported before as data resource and profile fungal community by sequencing ITS amplicons at the critical stages of limb regeneration (0–1–4–7–30–60 days post amputation, ‘dpa’). Results reveal a decline in richness and evenness in the course of limb regeneration, with bacterial community richness recovering beyond 30 dpa unlike fungi community. Beta diversity analysis reveals precise restructuring of the bacterial community along the three phases of limb regeneration, contrasting with less congruent changes in the fungal community. Temporal dynamics of the bacterial community highlight prevalent anaerobic bacteria in initiation phase and Flavobacterium bloom in the early phase correlating with limb blastema proliferation. Predicted functional analysis mirrors these shifts, emphasising a transition from amino acid metabolism to lipid metabolism control. Fungal communities shift from Blastomycota to Ascomycota dominance in the late regeneration stage. Our findings provide ecologically relevant insights into stage specific role of microbiome contributions to axolotl limb regeneration.Öğe Reduced resting and task-related alpha activity in mine workers: Implications for occupational health and neurodegenerative risk(2025) Çelik, Samet; Yıldırım, Ebru; Güntekin, BaharUnderground mine workers face many risk factors at work sites that are known to affect the neural system. Observational studies report that these risk factors precede neuromuscular and neurodegenerative disorders, especially in old-age miners. Neurodegenerative disorders have electrophysiological, anatomical, and functional changes long before symptoms are seen in older adults. Therefore, this study investigated whether risks faced by miners at young ages were reflected in electrophysiological signals. Twenty-one underground miners and twenty-two above-ground workers matched with them in terms of age, education, and working duration were included in this study. Participants were recorded with a 20-channel EEG during the resting-state (eyes open and closed; EO-EC) and the perception of the International Affective Picture System Paradigm (IAPS). Time-frequency analyses were performed for alpha frequency. Rs-EEG results showed a statistically significant difference in alpha power between the EO and EC states in the control group. However, there was no statistical difference in alpha power between these two conditions in the miners. Additionally, we noted a more pronounced decrease in alpha responses in the posterior region during EC in the miners. The group's main effects were statistically significant in event-related alpha responses during emotional responses. Accordingly, event-related alpha responses of the miner group were lower than the control group in terms of both power spectrum and phase-locking. Underground mine workers are cognitively and emotionally affected by risks in the work environment. Electrophysiological changes seen in young underground workers may be a harbinger of neurodegenerative disorders in miners' old age. Our research findings may lead to the development of occupational neuroscience, social policies, and worker health, which are necessary to improve working conditions for mineworkers.Öğe Design of balansens: functional evaluation in ankle preparation phase(2024) Ersoy, Tuğçe; Hocaoğlu, Elif; Kaya, Pınar; Ünal, RamazanIn this study, we present the design and development evaluation of BalanSENS toward the realization of the Integrated Balance Rehabilitation (I-BaR) framework. BalanSENS is designed to encourage active participation by integrating multi-sensory information with the co-improvement of sensory and motor functions. Moreover, it can offer individual rehabilitation design with the integration of three phases. The first phase provides foot-ankle muscle activation and movement sensation development. In the second phase, sensory weighting skills and upper extremities independence can be improved by using multi-sensory input. In the last/stepping phase, walking parameters are aimed to be improved with modulated distance. The parallel manipulator is designed through simulations to determine actuation properties and analyze the load-bearing capacity and feasibility of the materials. Drawing from simulation outcomes, an operational 3 DoF platform is constructed to demonstrate their design suitability for the I-BaR framework. Furthermore, design evaluations demonstrated promising results in quantifying force and real-time data monitoring during the passive ankle preparation phase.Öğe Surface roughness on cementoenamel junction after rubber-dam clamp application(2025) Erden Kayalıdere, Ezgi; Şahin, Merve; Korkut, Bora; Müdok, Tangül; Çalışkan Yanıkoğlu, FundaObjective: To investigate the surface roughness on cementoenamel junction after application of various rubber-dam retraction clamps for different durations. Materials and Methods: Fifty-four extracted human molar teeth were used. Various retraction clamps were placed on the cementoenamel junction. There are three main examination groups in the study. Group 1 (n = 6) included a polymer clamp (SoftClamp, Kerr Hawe, Switzerland), Group 2 (n = 6) included a metal clamp with a flat edge (Black Line RDCM7X, Hu-Friedy Group, USA), and Group 3 (n = 6) included a metal clamp with a serrated edge (Fiesta Color Coded, Coltene, USA). All clamps were applied for 30 min, 1, and 2 h. Surface roughness measurements were performed using a profilometer before and after the clamp application and surface morphology was assessed through the SEM images. One-way ANOVA was used to compare three or more groups. Percentage changes were evaluated using the Kruskal–Wallis test, followed by Dunn's test for post hoc analyses. The deemed significance was set at p < 0.05. Results: Between the initial and the final roughness measurements, after 30 min of clamp application, only Group 3 showed significant increases in roughness (p = 0.001). After 1 and 2 h of clamp application, there were significant increases in roughness for all groups. No significant differences in percentage changes for all groups in 30 min and 2 h of application (p = 0.220 and p = 0.091, respectively). However, Group 1 presented significantly lower surface roughness in percentage after the 1 h of application (p = 0.040). No significant differences in the percentage changes in roughness were observed within the groups for 30 min, 1, and 2 h applications (p = 0.220, p = 0.884, and p = 0.755 for Groups 1, 2, and 3, respectively). In SEM analysis, deep point microstructure defects were seen as the clamp application time increased. Conclusions: Rubber-dam clamp application may cause damage to the cementoenamel junction area. However, the level of damage is clamp-type-dependent. Slight scratch-type damages were observed on teeth with plastic clamps, while metal clamps generally caused cracks. The increase in the duration of the same rubber-dam clamp application was not considered an effective factor regarding the damage. Clinical Significance: During rubber-dam isolation, clamp type and duration of the application may cause damage to the tooth surface or progress an existing defect. Examining the teeth before selecting the clamp might be beneficial for minimizing dental tissue damage.Öğe Design of balansens: functional evaluation in ankle preparation phase(2024) Ersoy, Tuğçe; Hocaoğlu, Elif; Kaya, Pınar; Ünal, RamazanIn this study, we present the design and development evaluation of BalanSENS toward the realization of the Integrated Balance Rehabilitation (I-BaR) framework. BalanSENS is designed to encourage active participation by integrating multi-sensory information with the co-improvement of sensory and motor functions. Moreover, it can offer individual rehabilitation design with the integration of three phases. The first phase provides foot-ankle muscle activation and movement sensation development. In the second phase, sensory weighting skills and upper extremities independence can be improved by using multi-sensory input. In the last/stepping phase, walking parameters are aimed to be improved with modulated distance. The parallel manipulator is designed through simulations to determine actuation properties and analyze the load-bearing capacity and feasibility of the materials. Drawing from simulation outcomes, an operational 3 DoF platform is constructed to demonstrate their design suitability for the I-BaR framework. Furthermore, design evaluations demonstrated promising results in quantifying force and real-time data monitoring during the passive ankle preparation phase.
