Browsing by Subject "Pathophysiology"

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Open Access
Application of the RIMARC algorithm to a large data set of action potentials and clinical parameters for risk prediction of atrial fibrillation
(Springer, 2015) Ravens, U.; Katircioglu-Öztürk, D.; Wettwer, E.; Christ, T.; Dobrev, D.; Voigt, N.; Poulet, C.; Loose, S.; Simon, J.; Stein, A.; Matschke, K.; Knaut, M.; Oto, E.; Oto, A.; Güvenir, H. A.
Ex vivo recorded action potentials (APs) in human right atrial tissue from patients in sinus rhythm (SR) or atrial fibrillation (AF) display a characteristic spike-and-dome or triangular shape, respectively, but variability is huge within each rhythm group. The aim of our study was to apply the machine-learning algorithm ranking instances by maximizing the area under the ROC curve (RIMARC) to a large data set of 480 APs combined with retrospectively collected general clinical parameters and to test whether the rules learned by the RIMARC algorithm can be used for accurately classifying the preoperative rhythm status. APs were included from 221 SR and 158 AF patients. During a learning phase, the RIMARC algorithm established a ranking order of 62 features by predictive value for SR or AF. The model was then challenged with an additional test set of features from 28 patients in whom rhythm status was blinded. The accuracy of the risk prediction for AF by the model was very good (0.93) when all features were used. Without the seven AP features, accuracy still reached 0.71. In conclusion, we have shown that training the machine-learning algorithm RIMARC with an experimental and clinical data set allows predicting a classification in a test data set with high accuracy. In a clinical setting, this approach may prove useful for finding hypothesis-generating associations between different parameters.
Open Access
Biosystems engineering of prokaryotes with tumor-killing capacities
(Bentham Science Publishers Ltd., 2016) Kalyoncu, E.; Olmez, T. T.; Ozkan, A. D.; Sarioglu, O. F.
Certain bacteria selectively attack tumor tissues and trigger tumor shrinkage by producing toxins and modulating the local immune system, but their clinical utility is limited because of the dangers posed by systemic infection. Genetic engineering can be used to minimize the risks associated with tumor-targeting pathogens, as well as to increase their efficiency in killing tumor cells. Advances in genetic circuit design have led to the development of bacterial strains with enhanced tumor-targeting capacities and the ability to secrete therapeutics, cytotoxic proteins and prodrug-cleaving enzymes, which allows their safe and effective use for cancer treatment. The present review details the recent advances in the design and application of these modified bacterial strains.
Open Access
BRAPH: A graph theory software for the analysis of brain connectivity
(Public Library of Science, 2017) Mijalkov, M.; Kakaei, E.; Pereira, J. B.; Westman, E.; Volpe, G.
The brain is a large-scale complex network whose workings rely on the interaction between its various regions. In the past few years, the organization of the human brain network has been studied extensively using concepts from graph theory, where the brain is represented as a set of nodes connected by edges. This representation of the brain as a connectome can be used to assess important measures that reflect its topological architecture. We have developed a freeware MatLab-based software (BRAPH–BRain Analysis using graPH theory) for connectivity analysis of brain networks derived from structural magnetic resonance imaging (MRI), functional MRI (fMRI), positron emission tomography (PET) and electroencephalogram (EEG) data. BRAPH allows building connectivity matrices, calculating global and local network measures, performing non-parametric permutations for group comparisons, assessing the modules in the network, and comparing the results to random networks. By contrast to other toolboxes, it allows performing longitudinal comparisons of the same patients across different points in time. Furthermore, even though a user-friendly interface is provided, the architecture of the program is modular (object-oriented) so that it can be easily expanded and customized. To demonstrate the abilities of BRAPH, we performed structural and functional graph theory analyses in two separate studies. In the first study, using MRI data, we assessed the differences in global and nodal network topology in healthy controls, patients with amnestic mild cognitive impairment, and patients with Alzheimer’s disease. In the second study, using resting-state fMRI data, we compared healthy controls and Parkinson’s patients with mild cognitive impairment. © 2017 Mijalkov 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.
Open Access
Diabetic wound regeneration using heparin-mimetic peptide amphiphile gel in db/db mice
(Royal Society of Chemistry, 2017) Senturk, Berna; Demircan, Burak M.; Ozkan, Alper D.; Tohumeken, Sehmus; Delibasi, T.; Güler, Mustafa O.; Tekinay, Ayse B.
There is an urgent need for more efficient treatment of chronic wounds in diabetic patients especially with a high risk of leg amputation. Biomaterials capable of presenting extracellular matrix-mimetic signals may assist in the recovery of diabetic wounds by creating a more conducive environment for blood vessel formation and modulating the immune system. In a previous study, we showed that glycosaminoglycan-mimetic peptide nanofibers are able to increase the rate of closure in STZ-induced diabetic rats by induction of angiogenesis. The present study investigates the effect of a heparin-mimetic peptide amphiphile (PA) nanofiber gel on full-thickness excisional wounds in a db/db diabetic mouse model, with emphasis on the ability of the PA nanofiber network to regulate angiogenesis and the expression of pro-inflammatory cytokines. Here, we showed that the heparin-mimetic PA gel can support tissue neovascularization, enhance the deposition of collagen and expression of alpha-smooth muscle actin (α-SMA), and eliminate the sustained presence of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the diabetic wound site. As the absence of neovascularization and overexpression of pro-inflammatory markers are a hallmark of diabetes and interfere with wound recovery by preventing the healing process, the heparin-mimetic PA treatment is a promising candidate for acceleration of diabetic wound healing by modulating angiogenesis and local immune response. © 2017 The Royal Society of Chemistry.
Open Access
Disrupted network topology in patients with stable and progressive mild cognitive impairment and alzheimer's disease
(Oxford University Press, 2016) Pereira, J. B.; Mijalkov, M.; Kakaei, E.; Mecocci, P.; Vellas, B.; Tsolaki, M.; Kłoszewska, I.; Soininen, H.; Spenger, C.; Lovestone, S.; Simmons, A.; Wahlund, L.-O.; Volpe, G.; Westman, E.
Recent findings suggest that Alzheimer's disease (AD) is a disconnection syndrome characterized by abnormalities in large-scale networks. However, the alterations that occur in network topology during the prodromal stages of AD, particularly in patients with stable mild cognitive impairment (MCI) and those that show a slow or faster progression to dementia, are still poorly understood. In this study, we used graph theory to assess the organization of structural MRI networks in stable MCI (sMCI) subjects, late MCI converters (lMCIc), early MCI converters (eMCIc), and AD patients from 2 large multicenter cohorts: ADNI and AddNeuroMed. Our findings showed an abnormal global network organization in all patient groups, as reflected by an increased path length, reduced transitivity, and increased modularity compared with controls. In addition, lMCIc, eMCIc, and AD patients showed a decreased path length and mean clustering compared with the sMCI group. At the local level, there were nodal clustering decreases mostly in AD patients, while the nodal closeness centrality detected abnormalities across all patient groups, showing overlapping changes in the hippocampi and amygdala and nonoverlapping changes in parietal, entorhinal, and orbitofrontal regions. These findings suggest that the prodromal and clinical stages of AD are associated with an abnormal network topology.
Open Access
The effect of epidural anesthesia on muscle flap tolerance to venous ischemia
(Lippincott Williams & Wilkins, 2010) Cayci, C.; Cinar, C.; Yucel, O. A.; Tekinay, T.; Ascherman, J. A.
Background: Venous ischemia is a major cause of failure after free tissue transfers and replantations. The combination of general and epidural anesthesia leads to vasodilatation and improves tissue perfusion. Postoperative pain relief and sympathetic blockage are additional benefits of epidural anesthesia. The purpose of this study was to determine whether epidural anesthesia has benefits on microcirculation and neutrophil functions in muscle flaps subjected to venous ischemia. Method: Thirty Sprague-Dawley rats were divided into three groups: group I, general anesthesia; group II, spinal anesthesia; and group III, epidural anesthesia. Cremaster flaps were prepared, postcapillary venules were selected under intravital videomicroscopy, and flaps were subjected to venous ischemia. Images were recorded from preselected postcapillary venules before venous ischemia (baseline) and following reperfusion. Neutrophil rolling and adhesion, functional capillary density, and diameters of postcapillary venules were evaluated. Results: The increase in rolling neutrophils in group III was significantly lower than in groups I and II at 60 and 120 minutes. Change of adherent neutrophils in group III was significantly lower than in groups I and II at 15, 60 and 120 minutes. There was significantly more reduction in inner diameter of postcapillary venules in groups I and II compared with group III. Functional capillary density in groups I and II was significantly lower than in group III. Conclusion: Epidural anesthesia regulated neutrophil functions, salvaged functional capillaries, and prevented vasoconstriction of postcapillary venules in cremaster muscle flaps subjected to venous ischemia. Spinal and general anesthesia, however, were found to be ineffective in improving microcirculation of muscle flaps subjected to venous ischemia.
Open Access
Evidence from autoimmune thyroiditis of skewed X-chromosome inactivation in female predisposition to autoimmunity
(Nature Publishing Group, 2006) Ozcelik, T.; Uz, E.; Akyerli, C. B.; Bagislar, S.; Mustafa, C. A.; Gursoy, A.; Akarsu, N.; Toruner, G.; Kamel, N.; Gullu, S.
The etiologic factors in the development of autoimmune thyroid diseases (AITDs) are not fully understood. We investigated the role of skewed X-chromosome inactivation (XCI) mosaicism in female predisposition to AITDs. One hundred and ten female AITDs patients (81 Hashimoto's thyroiditis (HT), 29 Graves' disease (GD)), and 160 female controls were analyzed for the androgen receptor locus by the HpaII/polymerase chain reaction assay to assess XCI patterns in DNA extracted from peripheral blood cells. In addition, thyroid biopsy, buccal mucosa, and hair follicle specimens were obtained from five patients whose blood revealed an extremely skewed pattern of XCI, and the analysis was repeated. Skewed XCI was observed in DNA from peripheral blood cells in 28 of 83 informative patients (34%) as compared with 10 of 124 informative controls (8% P<0.0001). Extreme skewing was present in 16 patients (19%), but only in three controls (2.4% P<60;0.0001). The buccal mucosa, and although less marked, the thyroid specimens also showed skewing. Analysis of two familial cases showed that only the affected individuals demonstrate skewed XCI patterns. Based on these results, skewed XCI mosaicism may play a significant role in the pathogenesis of AITDs.
Open Access
HER2 and proliferation of wound-induced breast carcinoma
(The Lancet Publishing, 2003-11-01) Tez, M.; Göçmen, E.; Özçelik, T.
Open Access
Ischemic stroke phenotype in patients with nonsustained atrial fibrillation
(Lippincott Williams and Wilkins, 2015) Arsava, E. M.; Bas, D. F.; Atalar, Ergin; Has, A. C.; Oguz, K. K.; Topcuoglu, M. A.
Background and Purpose: The widespread use of ambulatory cardiac monitoring has not only increased the detection of high-risk arrhythmias like persistent and paroxysmal atrial fibrillation (AF), but also made it possible to identify other aberrations such as short-lasting (<30 seconds) irregular runs of supraventricular tachycardia. Ischemic stroke phenotype might be helpful in understanding whether these nonsustained episodes play a similar role in stroke pathophysiology like their persistent and paroxysmal counterparts. Methods: In a consecutive series of patients with ischemic stroke, we retrospectively determined clinical and imaging features associated with nonsustained AF (n=126), defined as <30-second-lasting supraventricular tachyarrhythmias with irregular RR interval on 24-hour Holter monitoring, and compared them to patients with persistent/paroxysmal AF (n=239) and no AF (n=246). Results: Patients with persistent/paroxysmal AF significantly differed from patients with nonsustained AF by a higher prevalence of female sex (odds ratio [95% confidence interval], 1.8 [1.1-2.9]), coronary artery disease (1.9 [1.1-3.0]), and embolic imaging features (2.7 [1.1-6.5]), and lower frequency of smoking (0.4 [0.2-0.8]) and hyperlipidemia (0.5 [0.3-0.8]). In contrast, patients with no AF were younger (0.5 [0.4-0.6] per decade) and more likely to be male (1.7 [1.0-2.8]) in comparison with nonsustained AF population. The prevalence of nonsustained AF was similar among cryptogenic and noncryptogenic stroke patients (32% versus 29%). Voxel-wise comparison of lesion probability maps revealed no significant difference between cryptogenic stroke patients with and without nonsustained AF. Conclusions: Clinical features of patients with nonsustained AF exhibited an intermediary phenotype in between patients with persistent/paroxysmal AF and no AF. Furthermore, imaging features did not entirely resemble patterns observed in patients with longer durations of AF.
Open Access
Structural brain alterations of Down’s syndrome in early childhood evaluation by DTI and volumetric analyses
(Springer Verlag, 2017) Gunbey, H. P.; Bilgici, M. C.; Aslan, K.; Has, A. C.; Ogur, M. G.; Alhan, A.; Incesu, L.
Objectives: To provide an initial assessment of white matter (WM) integrity with diffusion tensor imaging (DTI) and the accompanying volumetric changes in WM and grey matter (GM) through volumetric analyses of young children with Down’s syndrome (DS). Methods: Ten children with DS and eight healthy control subjects were included in the study. Tract-based spatial statistics (TBSS) were used in the DTI study for whole-brain voxelwise analysis of fractional anisotropy (FA) and mean diffusivity (MD) of WM. Volumetric analyses were performed with an automated segmentation method to obtain regional measurements of cortical volumes. Results: Children with DS showed significantly reduced FA in association tracts of the fronto-temporo-occipital regions as well as the corpus callosum (CC) and anterior limb of the internal capsule (p < 0.05). Volumetric reductions included total cortical GM, cerebellar GM and WM volume, basal ganglia, thalamus, brainstem and CC in DS compared with controls (p < 0.05). Conclusion: These preliminary results suggest that DTI and volumetric analyses may reflect the earliest complementary changes of the neurodevelopmental delay in children with DS and can serve as surrogate biomarkers of the specific elements of WM and GM integrity for cognitive development. Key Points: • DS is the most common genetic cause of intellectual disability. • WM and GM structural alterations represent the neurological features of DS. • DTI may identify the earliest aging process changes. • DTI-volumetric analyses can serve as surrogate biomarkers of neurodevelopment in DS. © 2016, European Society of Radiology.