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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/3
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Publication Metadata only Therapeutic targets of probiotics in Parkinson disease: a systematic review of randomized controlled trials(Iran University of Medical Sciences, 2024) Atak, Elif Sina; Yildiz, Dilara; Kocaturk, Ruemeysa Rabia; Ozcan, Oznur Ozge; Erguzel, Turker Tekin; Karahan, Mesut; Tarhan, Nevzat; Temizyürek, Arzu; School of MedicineIntroduction: Parkinson disease is the world's second most prevalent neurological disease. In this disease, intracytoplasmic neuronal inclusions are observed in enteric neurons in the gastrointestinal tract, and the composition of the intestinal microbiome is altered. These changes correlate with the motor phenotype. A systematic review was conducted to determine the effect of using probiotics in Parkinson disease. Methods: Scopus, PubMed, Web of Science, the Cochrane Library, ScienceDirect, and Ov & imath;dLWW were searched until April 2021. A total of 27395 records were found according to inclusion and exclusion criteria with the following outcomes: Parkinson disease rating, oxidative stress, and gastrointestinal system markers. Data search, article selection, and data extraction assessments were performed according to the PRISMA (preferred reporting items for systematic reviews and meta -analyses) guidelines. The Jadad scale was used to rate the evidence's quality. Results: Our study information was gathered from 5 randomized controlled trials involving 350 individuals with Parkinson disease receiving probiotic supplements. Parkinson disease rating and non -motor symptoms test were performed in the samples. Also, oxidative stress (glutathione, malondialdehyde) and gastrointestinal system symptoms (bowel opening frequency, gut transit time, complete bowel movement, spontaneous bowel movements) were evaluated during 4-12 weeks of using probiotics in these patients. Conclusion: While all high -quality studies demonstrate improvement in disease symptoms of the patients, currently sufficient data are not available to recommend the use of probiotics for people with Parkinson disease in clinical practice.Publication Metadata only Comparison of bihemispheric and unihemispheric M1 transcranial direct current stimulations during physical therapy in subacute stroke patients: a randomized controlled trial(Elsevier France-Editions Scientifiques Medicales Elsevier, 2023) Youssef, Hussein; Mohamed, Nema Abd El-Hameed; Hamdy, Mohamed; Youssef, Hussein; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health SciencesBackground: Despite the central origin of stroke affecting the primary motor cortex M1, most physical and occupational rehabilitation programs focus on peripheral treatments rather than addressing the central origin of the problem. This highlights the urgent need for effective proto-cols to improve neurological rehabilitation and achieve better long-term functional outcomes. Objectives: Our hypothesis was that the bihemispheric delivery of transcranial direct current stimulation (tDCS) is superior to unihemispheric in enhancing motor function after stroke, in both the upper and lower extremities. Methods: 35 sub-acute ischemic stroke survivors were randomly divided into three groups: bihe-mispheric and unihemispheric treatment groups, or sham groups. Each participant received a 20-minute session of tDCS with an intensity of 2 mA during physical therapy sessions, three days a week, for four weeks. The outcomes were measured using Fugl-Meyer assessment scale, modi-fied Ashworth scale, Berg balance scale, and serum brain-derived neurotrophic factor (BDNF) levels. Results: One-way ANOVA test indicated a significant effect of both treatment protocols on the upper extremity (p = < 0.001) and lower extremity (p = .034) for motor measures, but there was no difference between the two (p = .939). Kruskal Wallis test for spasticity showed a significant improvement in both treatment groups for elbow (p = .036) and wrist flexors (p = .025), com-pared to the sham group. However, there was no statistically significant difference in spasticity between uni-and bihemispheric stimulation for elbow (p = .731) or wrist flexors (p = .910). Conclusion: There is no statistically significant difference in efficacy between bihemispheric and unihemispheric tDCS in patients presenting with acute ischemic stroke.Publication Metadata only Persistent genital arousal disorder as an atypical presenting symptom of central nervous system demyelinating disorder(Wolters Kluwer Medknow Publications, 2023) Üçem, Selen; Buluş, Eser; Erkol, Gökhan; School of Medicine; Koç University HospitalN/APublication Metadata only T-cell activation state differentially contributes to neuropsychiatric complications in women with HIV(Elsevier, 2022) Williams, Dionna W.; Flores, Bianca R.; Xu, Yanxun; Wang, Yuezhe; Yu, Danyang; Peters, Brandilyn A.; Adedimeji, Adebola; Wilson, Tracey E.; Merenstein, Daniel; Tien, Phyllis C.; Cohen, Mardge H.; Weber, Kathleen M.; Adimora, Adaora A.; Ofotokun, Igho; Fischl, Margaret; Turan, Janet; Laumet, Geoffroy; Landay, Alan L.; Dastgheyb, Raha M.; Gange, Stephen J.; Weiser, Sheri D.; Rubin, Leah H.; Department of Psychology; Turan, Bülent; Department of Psychology; College of Social Sciences and HumanitiesNeuropsychiatric complications are common among women with HIV (WWH). The pathophysiological mechanisms underlying these complications are not fully known but likely driven in part by immune modulation. We examined associations between T-cell activation states which are required to mount an effective immune response (activation, co-stimulation/normal function, exhaustion, senescence) and neuropsychiatric complications in WWH. 369 WWH (78% HIV RNA undetectable/<20cp/mL) enrolled in the Women's Interagency HIV Study completed neuropsychological testing and measures of depression (Center for Epidemiological Studies Depression Scale-CES-D), self-reported stress levels (Perceived Stress Scale-10), and post-traumatic stress (PTSD Checklist-Civilian Scale). Multiparametric flow cytometry evaluated T-cell activation state. Partial least squares regressions were used to examine T-cell phenotypes and neuropsychiatric outcome associations after confounder adjustment. In the total sample and among virally suppressed (VS)-WWH, CD4(+) T-cell exhaustion was associated with poorer learning and attention/working memory (P's < 0.05). In the total sample, CD4(+) T-cell activation was associated with better attention/working memory and CD8(+) T-cell co-stimulation and senescence was associated with poorer executive function (P's < 0.05). For mental health outcomes, in the total sample, CD4(+) T-cell activation was associated with more perceived stress and CD4(+) T-cell exhaustion was associated with less depressive symptoms (P's < 0.05). Among VS-WWH, CD4(+) senescence was associated with less perceive stress and CD8(+) T-cell co-stimulation and senescence was associated with higher depression (P's < 0.05). Together, results suggest the contribution of peripheral CD4(+) and CD8(+) T-cell activation status to neuropsychiatric complications in WWH.Publication Metadata only Stereological and electrophysiological evaluation of autonomic involvement in amyotrophic lateral sclerosis(Elsevier France-Editions Scientifiques Medicales Elsevier, 2022) Ozturk, Rustem; Karlsson, Pall; Hu, Xiaoli; Akdeniz, Esra; Isak, Baris; Sürücü, Hüseyin Selçuk; School of MedicineObjective: Previous studies have identified autonomic dysfunction in amyotrophic lateral sclerosis (ALS) using mostly neurophysiological techniques. In this study, stereological evaluation of autonomic fibers and sweat glands has been performed to identify structural evidence of autonomic denervation in patients with ALS. Methods: In this study, 29 ALS patients were compared to 29 controls using COMPASS-31 questionnaire, sympathetic skin response (SSR), and heart rate variability (HRV) at rest. From the same cohorts, 20 ALS patients and 15 controls were further evaluated using staining of autonomic nerve fibers and sweat glands in skin biopsies. SSR and resting HRV were repeated in the ALS patient cohort one year later. Results: COMPASS-31 total score, gastrointestinal- and urinary-sub scores were higher in ALS patients than controls (P = 0.004, P = 0.005, and P = 0.049, respectively). In the ALS patient cohort, SSR amplitudes in hands and feet were lower than in controls (P<0.0001 and P = 0.0009, respectively), but there was no difference in resting HRV (P>0.05). While there was no change in nerve fibers innervating sweat glands, their density was lower in ALS patients than controls, and semi-quantitative analysis also showed structural damage (P = 0.02 and P = 0.001, respectively). SSR and resting HRV of ALS patients remained stable during the one-year follow-up period (P>0.05). Discussion: Supporting abnormal neurophysiological tests, stereological analysis revealed direct evidence of autonomic denervation in ALS patients. However, the degenerative process in autonomic nerve fibers is relatively slow, compared to the rate of motor neuron degeneration in this condition.Publication Metadata only Identification of corneal and intra-epidermal axonal swellings in amyotrophic lateral sclerosis(Wiley, 2023) Turhan, Semra Akkaya; Karlsson, Pall; Ozun, Yuksel; Gunes, Hande; Toker, Ebru; Isak, Baris; Sürücü, Hüseyin Selçuk; School of MedicineIntroduction/Aims: In patients with amyotrophic lateral sclerosis (ALS), axonal spheroids in motor axons have been identified in post-mortem studies. In this study, axonal spheroids and swellings on C-fibers of ALS patients were investigated using corneal confocal microscopy (CCM) and skin biopsy, respectively.Methods: Thirty-one ALS patients and 20 healthy subjects were evaluated with CCM to assess corneal nerve-fiber length (CNFL), -fiber density (CNFD), -branch density (CNBD), dendritic cell (DC) density, and axonal spheroids originating from C-fibers (>100 mu m(2)). In addition, intraepidermal nerve fiber density (IENFD) and axonal swellings (>1.5 mu m) were assessed in skin biopsies obtained from the arms and legs of 22 patients and 17 controls.Results: In ALS patients, IENFD, CNFD, CNFL, and CNBD were not different from controls. The density of DCs and the number of patients with increased DC density were higher in ALS patients than controls (p = .0005 and p = .008). The number of patients with axonal spheroids was higher than controls (p = .03).Discussion: Evaluation of DCs and axonal bulbs in C-fibers of ALS patients could provide insights into pathophysiology or potentially serve as biomarkers in ALS.Publication Metadata only Baseline prepulse inhibition dependency of orexin A and REM sleep deprivation(Springer, 2024) Öz, Pınar; Kamali, Osman; Gör, Ceren; Uzbay, İsmail Tayfun; Saka, Hacer Begüm; Graduate School of Health SciencesRationalePrepulse inhibition (PPI) impairment reflects sensorimotor gating problems, i.e. in schizophrenia. This study aims to enlighten the role of orexinergic regulation on PPI in a psychosis-like model.ObjectivesIn order to understand the impact of orexinergic innervation on PPI and how it is modulated by age and baseline PPI (bPPI), chronic orexin A (OXA) injections was carried on non-sleep-deprived and sleep-deprived rats that are grouped by their bPPI.MethodsbPPI measurements were carried on male Wistar rats on P45 or P90 followed by grouping into low-PPI and high-PPI rats. The rats were injected with OXA twice per day for four consecutive days starting on P49 or P94, while the control groups received saline injections. 72 h REMSD was carried on via modified multiple platform technique on P94 and either OXA or saline was injected during REMSD. PPI tests were carried out 30 min. after the last injection.ResultsOur previous study with acute OXA injection after REMSD without bPPI grouping revealed that low OXA doses might improve REMSD-induced PPI impairment. Our current results present three important conclusions: (1) The effect of OXA on PPI is bPPI-dependent and age-dependent. (2) The effect of REMSD is bPPI-dependent. (3) The effect of OXA on PPI after REMSD also depends on bPPI.ConclusionOrexinergic regulation of PPI response with and without REMSD can be predicted by bPPI levels. Our findings provide potential insights into the regulation of sensorimotor gating by sleep/wakefulness systems and present potential therapeutic targets for the disorders, where PPI is disturbed.Publication Metadata only Machine-learning-based prediction of disability progression in multiple sclerosis: an observational, international, multi-center study(Public Library of Science, 2024) De Brouwer, Edward; Becker, Thijs; Werthen-Brabants, Lorin; Dewulf, Pieter; Iliadis, Dimitrios; Dekeyser, Cathérine; Laureys, Guy; Van Wijmeersch, Bart; Popescu, Veronica; Dhaene, Tom; Deschrijver, Dirk; Waegeman, Willem; De Baets, Bernard; Stock, Michiel; Horakova, Dana; Patti, Francesco; Izquierdo, Guillermo; Eichau, Sara; Girard, Marc; Prat, Alexandre; Lugaresi, Alessandra; Grammond, Pierre; Kalincik, Tomas; Alroughani, Raed; Grand’Maison, Francois; Skibina, Olga; Terzi, Murat; Lechner-Scott, Jeannette; Gerlach, Oliver; Khoury, Samia J.; Cartechini, Elisabetta; Van Pesch, Vincent; Sà, Maria José; Weinstock-Guttman, Bianca; Blanco, Yolanda; Ampapa, Radek; Spitaleri, Daniele; Solaro, Claudio; Maimone, Davide; Soysal, Aysun; Iuliano, Gerardo; Gouider, Riadh; Castillo-Triviño, Tamara; Sánchez-Menoyo, José Luis; Laureys, Guy; van der Walt, Anneke; Oh, Jiwon; Aguera-Morales, Eduardo; Al-Asmi, Abdullah; de Gans, Koen; Fragoso, Yara; Csepany, Tunde; Hodgkinson, Suzanne; Deri, Norma; Al-Harbi, Talal; Taylor, Bruce; Gray, Orla; Lalive, Patrice; Rozsa, Csilla; McGuigan, Chris; Kermode, Allan; Sempere, Angel Pérez; Mihaela, Simu; Simo, Magdolna; Hardy, Todd; Decoo, Danny; Hughes, Stella; Grigoriadis, Nikolaos; Sas, Attila; Vella, Norbert; Moreau, Yves; Peeters, Liesbet; Altıntaş, Ayşe; ; School of Medicine;Background Disability progression is a key milestone in the disease evolution of people with multiple sclerosis (PwMS). Prediction models of the probability of disability progression have not yet reached the level of trust needed to be adopted in the clinic. A common benchmark to assess model development in multiple sclerosis is also currently lacking. Methods Data of adult PwMS with a follow-up of at least three years from 146 MS centers, spread over 40 countries and collected by the MSBase consortium was used. With basic inclusion criteria for quality requirements, it represents a total of 15, 240 PwMS. External validation was performed and repeated five times to assess the significance of the results. Transparent Reporting for Individual Prognosis Or Diagnosis (TRIPOD) guidelines were followed. Confirmed disability progression after two years was predicted, with a confirmation window of six months. Only routinely collected variables were used such as the expanded disability status scale, treatment, relapse information, and MS course. To learn the probability of disability progression, state-of-the-art machine learning models were investigated. The discrimination performance of the models is evaluated with the area under the receiver operator curve (ROC-AUC) and under the precision recall curve (AUC-PR), and their calibration via the Brier score and the expected calibration error. All our preprocessing and model code are available at https://gitlab.com/edebrouwer/ms_benchmark, making this task an ideal benchmark for predicting disability progression in MS. Findings Machine learning models achieved a ROC-AUC of 0.71 ± 0.01, an AUC-PR of 0.26 ± 0.02, a Brier score of 0.1 ± 0.01 and an expected calibration error of 0.07 ± 0.04. The history of disability progression was identified as being more predictive for future disability progression than the treatment or relapses history. Conclusions Good discrimination and calibration performance on an external validation set is achieved, using only routinely collected variables. This suggests machine-learning models can reliably inform clinicians about the future occurrence of progression and are mature for a clinical impact study. Copyright: © 2024 De Brouwer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Publication Metadata only A systematic review and meta-analysis of social cognition among people living with HIV;implications for non-social cognition and social everyday functioning(Springer, 2024) Vance, David E.; Billings, Rebecca; Lambert, Crystal Chapman; Fazeli, Pariya L.; Goodin, Burel R.; Kempf, Mirjam-Colette; Rubin, Leah H.; Wise, Jenni; Hellemann, Gerhard; Lee, Junghee; Department of Psychology; Turan, Bülent; Department of Psychology; ; College of Social Sciences and Humanities;Social cognition-the complex mental ability to perceive social stimuli and negotiate the social environment-has emerged as an important cognitive ability needed for social functioning, everyday functioning, and quality of life. Deficits in social cognition have been well documented in those with severe mental illness including schizophrenia and depression, those along the autism spectrum, and those with other brain disorders where such deficits profoundly impact everyday life. Moreover, subtle deficits in social cognition have been observed in other clinical populations, especially those that may have compromised non-social cognition (i.e., fluid intelligence such as memory). Among people living with HIV (PLHIV), 44% experience cognitive impairment; likewise, social cognitive deficits in theory of mind, prosody, empathy, and emotional face recognition/perception are gradually being recognized. This systematic review and meta-analysis aim to summarize the current knowledge of social cognitive ability among PLHIV, identified by 14 studies focused on social cognition among PLHIV, and provides an objective consensus of the findings. In general, the literature suggests that PLHIV may be at-risk of developing subtle social cognitive deficits that may impact their everyday social functioning and quality of life. The causes of such social cognitive deficits remain unclear, but perhaps develop due to (1) HIV-related sequelae that are damaging the same neurological systems in which social cognition and non-social cognition are processed; (2) stress related to coping with HIV disease itself that overwhelms one's social cognitive resources; or (3) may have been present pre-morbidly, possibly contributing to an HIV infection. From this, a theoretical framework is proposed highlighting the relationships between social cognition, non-social cognition, and social everyday functioning.Publication Metadata only Neuronal ensembles: Building blocks of neural circuits(Cell Press, 2024) Yuste, Rafael; Cossart, Rosa; Yakşi, Emre; ; School of Medicine;Neuronal ensembles, defined as groups of neurons displaying recurring patterns of coordinated activity, represent an intermediate functional level between individual neurons and brain areas. Novel methods to measure and optically manipulate the activity of neuronal populations have provided evidence of ensembles in the neocortex and hippocampus. Ensembles can be activated intrinsically or in response to sensory stimuli and play a causal role in perception and behavior. Here we review ensemble phenomenology, developmental origin, biophysical and synaptic mechanisms, and potential functional roles across different brain areas and species, including humans. As modular units of neural circuits, ensembles could provide a mechanistic underpinning of fundamental brain processes, including neural coding, motor planning, decision-making, learning, and adaptability. © 2023 Elsevier Inc.