Examination of the Complex Molecular Landscape in Obesity and Type 2 Diabetes.

The escalating prevalence of metabolic disorders, notably type 2 diabetes (T2D) and obesity, presents a critical global health challenge, necessitating deeper insights into their molecular underpinnings. Our study integrates proteomics and metabolomics analyses to delineate the complex molecular landscapes associated with T2D and obesity. Leveraging data from 130 subjects, including individuals with T2D and obesity as well as healthy controls, we elucidate distinct molecular signatures and identify novel biomarkers indicative of disease progression. Our comprehensive characterization of cardiometabolic proteins and serum metabolites unveils intricate networks of biomolecular interactions and highlights differential protein expression patterns between T2D and obesity cohorts. Pathway enrichment analyses reveal unique mechanisms underlying disease development and progression, while correlation analyses elucidate the interplay between proteomics, metabolomics, and clinical parameters. Furthermore, network analyses underscore the interconnectedness of cardiometabolic proteins and provide insights into their roles in disease pathogenesis. Our findings may help to refine diagnostic strategies and inform the development of personalized interventions, heralding a new era in precision medicine and healthcare innovation. Through the integration of multi-omics approaches and advanced analytics, our study offers a crucial framework for deciphering the intricate molecular underpinnings of metabolic disorders and paving the way for transformative therapeutic strategies.

Comparison of pre-mortem 2D-3D ultrasound examination to post-mortem micro-CT of carotid arteries - first experiences.

Background and purpose:

A prerequisite for the treatment of carotid atherosclerosis is the accurate measurement of the stenosis, that is most commonly evaluated by duplex ultrasonography. In this study, we aimed to verify the reliability of 2D and 3D ultrasonography, comparing the data to results of post-mortem micro-CT examination.

Neurological patients with any life-threatening, presumably fatal neurological disease were enrolled. Ultrasound examinations were performed with a Philips Epiq 5G machine, using a VL13-5 broadband linear volume array transducer. Plaque length, diameter and vessel area reduction (stenosis) were calculated using the 2D images. Finally, the stenosis was reassessed using automatized, 3D application as well. After the death of the patient, autopsy was performed, during which the previously examined carotid artery was removed. The samples were examined with micro-CT. Similar to the ultrasound examination, plaque length, diameter and vessel area reduction (stenosis) were determined.

Ten vessels of seven patients were eligible for complex comparison. Plaque diameter and length measured by CT did not correlate with the ultrasound data. CT-measured axial plaque and vessel areas showed no correlation with ultrasound results either. While determining the strength of correlation between stenoses measured by the different modalities, significant correlation was found between the results measured by ultrasound (2D) and CT (Pearson r: 0.902, P<0.001).

Three-dimensional ultrasound analysis is a spectacular method for examining carotid plaques, as it can assist in a more detailed evaluation of the plaque morphology and composition, thereby identifying plaques with a particularly high risk of stroke. Micro-CT is an excellent tool for the exact determination of calcified plaque areas, but ultrasound images are not suitable yet for such a precise examination due to acoustic shadowing and artifacts.

In Vivo Evaluation of Brain [18F]F-FDG Uptake Pattern Under Different Anaesthesia Protocols.

BACKGROUND/AIM: Since the use of anaesthetics has the drawback of altering radiotracer distribution, preclinical positron emission tomography (PET) imaging findings of anaesthetised animals must be carefully handled. This study aimed at assessing the cerebral [18F]F-FDG uptake pattern in healthy Wistar rats under four different anaesthesia protocols using microPET/magnetic resonance imaging (MRI) examinations. MATERIALS AND METHODS: Post-injection of 15±1.2 MBq of [18F]F-FDG, either while awake or during the isoflurane-induced incubation phase was applied. Prior to microPET/MRI imaging, one group of the rats was subjected to forane-only anaesthesia while the other group was anaesthetised with the co-administration of forane and dexmedetomidine/Dexdor® Results: While as for the whole brain it was the addition of dexmedetomidine/Dexdor® to the anaesthesia protocol that generated the differences between the radiotracer concentrations of the investigated groups, regarding the cortex, the [18F]F-FDG accumulation was rather affected by the way of incubation. To ensure the most consistent and highest uptake, forane-induced anaesthesia coupled with an awake uptake condition seemed to be most suitable method of anaesthetisation for cerebral metabolic assessment. Diminished whole brain and cortical tracer accumulation detected upon dexmedetomidine/Dexdor® administration highlights the significance of the mechanism of action of different anaesthetics on radiotracer pharmacokinetics. CONCLUSION: Overall, the standardization of PET protocols is of utmost importance to avoid the confounding factors derived from anaesthesia.

[Coding of laboratory parameters using the LOINC system at the Clinical Center of the University of Debrecen]. / Laboratóriumi paraméterek kódolása a LOINC-rendszer szerint a Debreceni Egyetem Klinikai Központjában.

INTRODUCTION: The research utility of the bulk of the medical data generated at the Clinical Center of the University of Debrecen, which is constituted mainly by the clinical diagnostic laboratory results and medical images, is quite constrained in its present unstandardized form. The primary aim of the Big Data Research and Development project at the University of Debrecen is to facilitate data transformation and standardization to propagate its research utility for the potential end-users. Data generated in the in vitro diagnostic laboratory setting are an ideal candidate for the aforementioned goals. Data generated in Hungarian language in this particular setting are typically acronyms that do not particularly confirm to any standard norms and the transformation of these data using the globally acknowledged Logical Observation Identifiers Names and Codes (LOINC) was the primary goal of this research project. Globally the LOINC is used by healthcare providers, government agencies, insurance companies, software and device manufacturers, researchers and reference laboratories for identifying medical laboratory observations and promote unhindered fluency between various systems. OBJECTIVE: The aim of the project was to assure compliance of the various routine diagnostic laboratory parameters (n = 448) generated at the Department of Laboratory Medicine of the University of Debrecen to the LOINC system paying particular attention to and accommodating data sensitive to timeline and methodology. METHODS: Keywords allocated to individual parameters determined by the laboratory were provided by the IT service provider of the facility. The individual codes for the various parameters were manually identified using the search engine of the LOINC database available at http://www.loinc.org, only upon attainment of proficiency in use of the database and ample familiarity with the scientific literature on the topic. RESULTS: All routine diagnostic laboratory parameters were LOINC coded with no exception. The list of LOINCs' was made available on the https://labmed.unideb.hu/hu/loinc-tablazatok web link of the University of Debrecen. CONCLUSION: The transformation of diagnostic laboratory parameters to globally recognized LOINCs' improves and further facilitates the international integration of data generated at the University of Debrecen, furthermore propels communications between laboratories and parties of interest beyond international boundaries and borders. Orv Hetil. 2023; 164(27): 1043-1051.

Epileptic diathesis: An EEG-LORETA study.

OBJECTIVE: Epileptic diathesis is an inherited neurophysiological trait that contributes to the development of all types of epilepsy. The amount of resting-state electroencephalography (EEG) theta activity is proportional to the degree of cortical excitability and epileptic diathesis. Our aim was to explore the amount and topographic distribution of theta activity in epilepsy groups. We hypothesized that the anatomical distribution of increased theta activity is independent of the epilepsy type. METHODS: Patients with unmedicated idiopathic generalized epilepsy (IGE, n = 92) or focal epilepsy (FE, n = 149) and non-seizure patients with mild to moderate cerebral lesions (NONEP, n = 99) were compared to healthy controls (NC, n = 114). We analysed artifact-free EEG activity and defined multiple distributed sources of theta activity in the source space via low resolution electromagnetic tomography software. Age-corrected and Z-transformed theta values were compared across the groups. RESULTS: The rank of increased theta activity was IGE > FE > NONEP > NC. Both epilepsy groups showed significantly more theta activity than did the NC group. Maximum theta abnormality occurred in the medial-basal prefrontal and anterior temporal cortex in both epilepsy groups. CONCLUSIONS: We confirmed the hypothesis outlined above. SIGNIFICANCE: The common topographical pattern of increased EEG theta activity is correlated with epileptic diathesis, regardless of the epilepsy type.

Oxyhemoglobin and Cerebral Blood Flow Transients Detect Infarction in Rat Focal Brain Ischemia.

Spreading depolarizations (SD) refer to the near-complete depolarization of neurons that is associated with brain injuries such as ischemic stroke. The present gold standard for SD monitoring in humans is invasive electrocorticography (ECoG). A promising non-invasive alternative to ECoG is diffuse optical monitoring of SD-related flow and hemoglobin transients. To investigate the clinical utility of flow and hemoglobin transients, we analyzed their association with infarction in rat focal brain ischemia. Optical images of flow, oxy-hemoglobin, and deoxy-hemoglobin were continuously acquired with Laser Speckle and Optical Intrinsic Signal imaging for 2 h after photochemically induced distal middle cerebral artery occlusion in Sprague-Dawley rats (n = 10). Imaging was performed through a 6 × 6 mm window centered 3 mm posterior and 4 mm lateral to Bregma. Rats were sacrificed after 24 h, and the brain slices were stained for assessment of infarction. We mapped the infarcted area onto the imaging data and used nine circular regions of interest (ROI) to distinguish infarcted from non-infarcted tissue. Transients propagating through each ROI were characterized with six parameters (negative, positive, and total amplitude; negative and positive slope; duration). Transients were also classified into three morphology types (positive monophasic, biphasic, negative monophasic). Flow transient morphology, positive amplitude, positive slope, and total amplitude were all strongly associated with infarction (p < 0.001). Associations with infarction were also observed for oxy-hemoglobin morphology, oxy-hemoglobin positive amplitude and slope, and deoxy-hemoglobin positive slope and duration (all p < 0.01). These results suggest that flow and hemoglobin transients accompanying SD have value for detecting infarction.

Topological dissimilarities of hierarchical resting networks in type 2 diabetes mellitus and obesity.

Type 2 diabetes mellitus (T2DM) is reported to cause widespread changes in brain function, leading to cognitive impairments. Research using resting-state functional magnetic resonance imaging data already aims to understand functional changes in complex brain connectivity systems. However, no previous studies with dynamic causal modelling (DCM) tried to investigate large-scale effective connectivity in diabetes. We aimed to examine the differences in large-scale resting state networks in diabetic and obese patients using combined DCM and graph theory methodologies. With the participation of 70 subjects (43 diabetics, 27 obese), we used cross-spectra DCM to estimate connectivity between 36 regions, subdivided into seven resting networks (RSN) commonly recognized in the literature. We assessed group-wise connectivity of T2DM and obesity, as well as group differences, with parametric empirical Bayes and Bayesian model reduction techniques. We analyzed network connectivity globally, between RSNs, and regionally. We found that average connection strength was higher in T2DM globally and between RSNs, as well. On the network level, the salience network shows stronger total within-network connectivity in diabetes (8.07) than in the obese group (4.02). Regionally, we measured the most significant average decrease in the right middle temporal gyrus (-0.013 Hz) and the right inferior parietal lobule (-0.01 Hz) relative to the obese group. In comparison, connectivity increased most notably in the left anterior prefrontal cortex (0.01 Hz) and the medial dorsal thalamus (0.009 Hz). In conclusion, we find the usage of complex analysis of large-scale networks suitable for diabetes instead of focusing on specific changes in brain function.

Comparative Analysis of Differential Cellular Transcriptome and Proteome Regulation by HIV-1 and HIV-2 Pseudovirions in the Early Phase of Infection.

In spite of the similar structural and genomic organization of human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2), striking differences exist between them in terms of replication dynamics and clinical manifestation of infection. Although the pathomechanism of HIV-1 infection is well characterized, relatively few data are available regarding HIV-2 viral replication and its interaction with host-cell proteins during the early phase of infection. We utilized proteo-transcriptomic analyses to determine differential genome expression and proteomic changes induced by transduction with HIV-1/2 pseudovirions during 8, 12 and 26 h time-points in HEK-293T cells. We show that alteration in the cellular milieu was indeed different between the two pseudovirions. The significantly higher number of genes altered by HIV-2 in the first two time-points suggests a more diverse yet subtle effect on the host cell, preparing the infected cell for integration and latency. On the other hand, GO analysis showed that, while HIV-1 induced cellular oxidative stress and had a greater effect on cellular metabolism, HIV-2 mostly affected genes involved in cell adhesion, extracellular matrix organization or cellular differentiation. Proteomics analysis revealed that HIV-2 significantly downregulated the expression of proteins involved in mRNA processing and translation. Meanwhile, HIV-1 influenced the cellular level of translation initiation factors and chaperones. Our study provides insight into the understudied replication cycle of HIV-2 and enriches our knowledge about the use of HIV-based lentiviral vectors in general.

In Vivo Imaging of Neo-angiogenesis of Transplanted Metastases in Subrenal Capsule Assay Induced Rat Model.

BACKGROUND/AIM: Changes in the expression of neo-angiogenic molecules in the primary tumor and its metastases may significantly affect the efficacy of therapies. The aim of this study was to evaluate the alterations in aminopeptidase N (APN/CD13) and αvß3 integrin receptor expression in serially transplanted mesoblastic nephroma tumor (Ne/De) metastases using 68Gallium (68Ga)-labeled NOTA-cNGR and NODAGA-RGD radiotracers and preclinical positron emission tomography (PET) imaging. MATERIALS AND METHODS: Primary and metastatic mesoblastic nephroma (Ne/De) tumors were induced by subrenal capsule assay (SRCA) in Fischer-344 rats. In vivo PET imaging experiments were performed 8±1 days after the SRCA surgery using intravenously injected 68Ga-NOTA-c(NGR), 68Ga-NODAGA-RGD, and [18F]FDG radiotracers. RESULTS: Among the examined neo-angiogenic molecules, the expression of αvß3 integrin in the tumors was significantly lower than that of APN/CD13. This observation was confirmed by the PET data analysis, where a 2-6-fold higher APN/CD13-specific 68Ga-NOTA-cNGR accumulation was observed in both primary malignancies and metastases. However, a steadily increased accumulation of [18F]FDG, 68Ga-NODAGA-RGD, and 68Ga-NOTA-cNGR was observed in the tumors growing under the renal capsule and in the metastatic parathymic lymph nodes during serial transplantations. The observed increase in 68Ga- NOTA-cNGR accumulation during serial transplantations correlated well with the western blot analysis, where APN/CD13 protein levels were also elevated in the metastatic parathymic lymph nodes. CONCLUSION: The observed increase in glucose metabolism and the up-regulated expression of αvß3 integrin and APN/CD13 during serial transplantations of metastases may indicate enhanced malignancy.

Metabolomic Analysis of Serum and Tear Samples from Patients with Obesity and Type 2 Diabetes Mellitus.

Metabolomics strategies are widely used to examine obesity and type 2 diabetes (T2D). Patients with obesity (n = 31) or T2D (n = 26) and sex- and age-matched controls (n = 28) were recruited, and serum and tear samples were collected. The concentration of 23 amino acids and 10 biogenic amines in serum and tear samples was analyzed. Statistical analysis and Pearson correlation analysis along with network analysis were carried out. Compared to controls, changes in the level of 6 analytes in the obese group and of 10 analytes in the T2D group were statistically significant. For obesity, the energy generation, while for T2D, the involvement of NO synthesis and its relation to insulin signaling and inflammation, were characteristic. We found that BCAA and glutamine metabolism, urea cycle, and beta-oxidation make up crucial parts of the metabolic changes in T2D. According to our data, the retromer-mediated retrograde transport, the ethanolamine metabolism, and, consequently, the endocannabinoid signaling and phospholipid metabolism were characteristic of both conditions and can be relevant pathways to understanding and treating insulin resistance. By providing potential therapeutic targets and new starting points for mechanistic studies, our results emphasize the importance of complex data analysis procedures to better understand the pathomechanism of obesity and diabetes.

PET/MRI in the Presurgical Evaluation of Patients with Epilepsy: A Concordance Analysis.

The aim of our prospective study was to evaluate the clinical impact of hybrid [18F]-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ([18F]-FDG PET/MRI) on the decision workflow of epileptic patients with discordant electroclinical and MRI data. A novel mathematical model was introduced for a clinical concordance calculation supporting the classification of our patients by subgroups of clinical decisions. Fifty-nine epileptic patients with discordant clinical and diagnostic results or MRI negativity were included in this study. The diagnostic value of the PET/MRI was compared to other modalities of presurgical evaluation (e.g., electroclinical data, PET, and MRI). The results of the population-level statistical analysis of the introduced data fusion technique and concordance analysis demonstrated that this model could be the basis for the development of a more accurate clinical decision support parameter in the future. Therefore, making the establishment of "invasive" (operable and implantable) and "not eligible for any further invasive procedures" groups could be much more exact. Our results confirmed the relevance of PET/MRI with the diagnostic algorithm of presurgical evaluation. The introduction of a concordance analysis could be of high importance in clinical and surgical decision-making in the management of epileptic patients. Our study corroborated previous findings regarding the advantages of hybrid PET/MRI technology over MRI and electroclinical data.

Association of plasma tryptophan concentration with periaqueductal gray matter functional connectivity in migraine patients.

Altered periaqueductal gray matter (PAG) functional connectivity contributes to brain hyperexcitability in migraine. Although tryptophan modulates neurotransmission in PAG projections through its metabolic pathways, the effect of plasma tryptophan on PAG functional connectivity (PAG-FC) in migraine has not been investigated yet. In this study, using a matched case-control design PAG-FC was measured during a resting-state functional magnetic resonance imaging session in migraine without aura patients (n = 27) and healthy controls (n = 27), and its relationship with plasma tryptophan concentration (TRP) was assessed. In addition, correlations of PAG-FC with age at migraine onset, migraine frequency, trait-anxiety and depressive symptoms were tested and the effect of TRP on these correlations was explored. Our results demonstrated that migraineurs had higher TRP compared to controls. In addition, altered PAG-FC in regions responsible for fear-cascade and pain modulation correlated with TRP only in migraineurs. There was no significant correlation in controls. It suggests increased sensitivity to TRP in migraine patients compared to controls. Trait-anxiety and depressive symptoms correlated with PAG-FC in migraine patients, and these correlations were modulated by TRP in regions responsible for emotional aspects of pain processing, but TRP did not interfere with processes that contribute to migraine attack generation or attack frequency.

Central Nervous System Involvement in Primary Sjögren's Syndrome: Narrative Review of MRI Findings.

Central nervous system (CNS) involvement is one of the numerous extraglandular manifestations of primary Sjögren's syndrome (pSS). Moreover, neurological complaints precede the sicca symptoms in 25-60% of the cases. We review the magnetic resonance imaging (MRI) lesions typical for pSS, involving the conventional examination, volumetric and morphometric studies, diffusion tensor imaging (DTI) and resting-state fMRI. The most common radiological lesions in pSS are white matter hyperintensities (WMH), scattered alterations hyperlucent on T2 and FLAIR sequences, typically located periventricularly and subcortically. Cortical atrophy and ventricular dilatation can also occur in pSS. Whilst these conditions are thought to be more common in pSS than healthy controls, DTI and resting-state fMRI alterations demonstrate evident microstructural changes in pSS. As pSS is often accompanied by cognitive symptoms, these MRI alterations are expectedly related to them. This relationship is not clearly delineated in conventional MRI studies, but DTI and resting-state fMRI examinations show more convincing correlations. In conclusion, the CNS manifestations of pSS do not follow a certain pattern. As the link between the MRI lesions and clinical manifestations is not well established, more studies involving larger populations should be performed to elucidate the correlations.

Homocysteine-related alterations of 18F-FDG brain pattern in metabolic diseases.

Since hyperhomocysteinaemia (HHcys) is implicated as a risk factor for the development of neurodegeneration, and is associated with the development of metabolic diseases,we aimed at analysing the effect of homocysteine (Hcys) on regional fluorine-18-fluorodeoxyglucose (18F-FDG) brain metabolismin 51 controlled type 2 diabetic and in 48 non-DM obese participants. Plasma Hcys levels were measured by an immunoassay. Homocysteine-related 18F-FDG regional brain metabolism was evaluated applying 18F-FDG PET/CT using magnetic resonance imaging (MRI)-based brain template for statistical parametric mapping (SPM) analysis. Homocysteine-related decreased 18F-FDG uptake was shown in the right middle temporal gyrus in the whole population. Diabetics with Hcys above the reference limit expressed decreased glucose metabolismin the left calcarine cortex compared to the obese with HHcys. Regional metabolic alterations evoked on the basis of HHcys draw attention to the potential risk of neurodegeneration caused by metabolic disturbances.

Cellular Proteo-Transcriptomic Changes in the Immediate Early-Phase of Lentiviral Transduction.

Lentivirus-based vectors derived from human immunodeficiency viruses type 1 and 2 (HIV-1 and 2) are widely used tools in research and may also be utilized in clinical settings. Like their parental virions, they are known to depend on the cellular machinery for successful gene delivery and integration. While most of the studies on cellular proteomic and transcriptomic changes have focused on the late phase of the transduction, studies of those changes in early time-points, especially in the case of HIV-2 based vectors, are widely lacking. Using second generation HIV-1 and 2 vesicular stomatitis virus G protein (VSV-G) pseudotyped lentiviral vectors, we transduced HEK-293T human embryonic kidney cells and carried out transcriptomic profiling at 0 and 2 h time points, with accompanying proteomic analysis at 2 h following transduction. Significant variations were observed in gene expression profile between HIV-1 and HIV-2 transduced samples. Thrombospondin 1 (THBS1), collagens (COL1A2, COL3A1), and eukaryotic translation factors (EIF3CL) in addition to various genes coding for long non-coding RNA (lncRNA) were significantly upregulated 2 h after HIV-2 transduction compared to HIV-1. Label-free quantification mass spectrometry (MS) indicated that seven proteins involved in RNA binding, mRNA transport, and chaperoning were significantly downregulated. The identification of cellular protein targets of lentiviral vectors and their effect on the cellular transcriptome will undoubtedly shed more light on their complex life cycle and may be utilized against infection by their parental lentiviruses. Furthermore, characterizing the early phase of HIV-2 infection may aid in the understanding of its pathomechanism and long incubation period.

The role of hybrid FDG-PET/MRI on decision-making in presurgical evaluation of drug-resistant epilepsy.

BACKGROUND: When MRI fails to detect a potentially epileptogenic lesion, the chance of a favorable outcome after epilepsy surgery becomes significantly lower (from 60 to 90% to 20-65%). Hybrid FDG-PET/MRI may provide additional information for identifying the epileptogenic zone. We aimed to investigate the possible effect of the introduction of hybrid FDG-PET/MRI into the algorithm of the decision-making in both lesional and non-lesional drug-resistant epileptic patients. METHODS: In a prospective study of patients suffering from drug-resistant focal epilepsy, 30 nonlesional and 30 lesional cases with discordant presurgical results were evaluated using hybrid FDG-PET/MRI. RESULTS: The hybrid imaging revealed morphological lesion in 18 patients and glucose hypometabolism in 29 patients within the nonlesional group. In the MRI positive group, 4 patients were found to be nonlesional, and in 9 patients at least one more epileptogenic lesion was discovered, while in another 17 cases the original lesion was confirmed by means of hybrid FDG-PET/MRI. As to the therapeutic decision-making, these results helped to indicate resective surgery instead of intracranial EEG (iEEG) monitoring in 2 cases, to avoid any further invasive diagnostic procedures in 7 patients, and to refer 21 patients for iEEG in the nonlesional group. Hybrid FDG-PET/MRI has also significantly changed the original therapeutic plans in the lesional group. Prior to the hybrid imaging, a resective surgery was considered in 3 patients, and iEEG was planned in 27 patients. However, 3 patients became eligible for resective surgery, 6 patients proved to be inoperable instead of iEEG, and 18 cases remained candidates for iEEG due to the hybrid FDG-PET/MRI. Two patients remained candidates for resective surgery and one patient became not eligible for any further invasive intervention. CONCLUSIONS: The results of hybrid FDG-PET/MRI significantly altered the original plans in 19 of 60 cases. The introduction of hybrid FDG-PET/MRI into the presurgical evaluation process had a potential modifying effect on clinical decision-making. TRIAL REGISTRATION: Trial registry: Scientific Research Ethics Committee of the Medical Research Council of Hungary. TRIAL REGISTRATION NUMBER: 008899/2016/OTIG . Date of registration: 08 February 2016.

Reduced Level of Tear Antimicrobial and Immunomodulatory Proteins as a Possible Reason for Higher Ocular Infections in Diabetic Patients.

(1) Background: Diabetes mellitus is one of the most common metabolic disorders and a risk factor for bacterial ocular infections. Our aim was to examine the antibacterial activity of tears from patients with diabetes mellitus with and without diabetic retinopathy and to link this activity to the level of tear proteins. (2) Methods: Non-stimulated basal tears were collected from 39 eyes of 35 subjects. The antibacterial activity of tear pools was tested against pathogenic Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 26922 and Pseudomonas aeruginosa ATCC 27853 strains. The levels of 10 antimicrobial and immunomodulatory proteins were analyzed in the individual tear samples of the studied groups by SRM-based targeted mass spectrometry analysis. (3) Results: Disease stage-specific antimicrobial effect was observed in case of Staphylococcus aureus ATCC 29213 strain, and a non-disease specific inhibitory effect was observed in case of Pseudomonas aeruginosa ATCC 27853 strain. Changes in the levels of the studied antimicrobial and immunomodulatory proteins in the tears of the studied groups were also observed. (4) Conclusions: The higher ocular infection rate observed in diabetic patients may be the consequence of the decreased antimicrobial activity of tears possibly caused by the changes in the levels of antimicrobial and immunomodulatory proteins.

Automated procedure assessing the accuracy of HRCT-PET registration applied in functional virtual bronchoscopy.

BACKGROUND: Bronchoscopy serves as direct visualisation of the airway. Virtual bronchoscopy provides similar visual information using a non-invasive imaging procedure(s). Early and accurate image-guided diagnosis requires the possible highest performance, which might be approximated by combining anatomical and functional imaging. This communication describes an advanced functional virtual bronchoscopic (fVB) method based on the registration of PET images to high-resolution diagnostic CT images instead of low-dose CT images of lower resolution obtained from PET/CT scans. PET/CT and diagnostic CT data were collected from 22 oncological patients to develop a computer-aided high-precision fVB. Registration of segmented images was performed using elastix. RESULTS: For virtual bronchoscopy, we used an in-house developed segmentation method. The quality of low- and high-dose CT image registrations was characterised by expert's scoring the spatial distance of manually paired corresponding points and by eight voxel intensity-based (dis)similarity parameters. The distribution of (dis)similarity parameter correlating best with anatomic scoring was bootstrapped, and 95% confidence intervals were calculated separately for acceptable and insufficient registrations. We showed that mutual information (MI) of the eight investigated (dis)similarity parameters displayed the closest correlation with the anatomy-based distance metrics used to characterise the quality of image registrations. The 95% confidence intervals of the bootstrapped MI distribution were [0.15, 0.22] and [0.28, 0.37] for insufficient and acceptable registrations, respectively. In case of any new patient, a calculated MI value of registered low- and high-dose CT image pair within the [0.28, 0.37] or the [0.15, 0.22] interval would suggest acceptance or rejection, respectively, serving as an aid for the radiologist. CONCLUSION: A computer-aided solution was proposed in order to reduce reliance on radiologist's contribution for the approval of acceptable image registrations.

Resting-state EEG theta activity reflects degree of genetic determination of the major epilepsy syndromes.

OBJECTIVE: To explore relationship between EEG theta activity and clinical data that imply the degree of genetic determination of epilepsy. METHODS: Clinical data of interest were epilepsy diagnosis and positive / negative family history of epilepsy. Study groups were: idiopathic generalized epilepsy (IGE), focal epilepsy (FE); FE of unknown etiology (FEUNK), FE of postnatal-acquired etiology (FEPA); all patients with positive / negative family history of epilepsy (FAPALL, FANALL, respectively), disregarding of the syndrome; FAP patients with 1st degree affected relative (FAP1) and those with 2nd degree epileptic relative only (FAP2). Quantitative EEG analysis assessed amount of theta (3.5-7.0 Hz) activity in 180 seconds of artifact-free waking EEG background activity for each patient and group. Group comparison was carried out by nonparametric statistics. RESULTS: Differences of theta activity were: FAPALL > FANALL (p = 0.01); FAP1 > FAP2 (p = 0.2752). IGE > FE (p = 0.02); FEUNK > FEPA (p = 0.07). CONCLUSIONS: This was the first attempt to explore and quantitatively ascertain relationship between an EEG variable and clinical data that imply greater or lesser degree of genetic determination in epilepsy. SIGNIFICANCE: Theta activity is endophenotype that bridges the gap between epilepsy susceptibility genes and clinical phenotypes. Amount of theta activity is indicative of degree of genetic determination of the epilepsies.

Characterizing Network Search Algorithms Developed for Dynamic Causal Modeling.

Dynamic causal modeling (DCM) is a widely used tool to estimate the effective connectivity of specified models of a brain network. Finding the model explaining measured data is one of the most important outstanding problems in Bayesian modeling. Using heuristic model search algorithms enables us to find an optimal model without having to define a model set a priori. However, the development of such methods is cumbersome in the case of large model-spaces. We aimed to utilize commonly used graph theoretical search algorithms for DCM to create a framework for characterizing them, and to investigate relevance of such methods for single-subject and group-level studies. Because of the enormous computational demand of DCM calculations, we separated the model estimation procedure from the search algorithm by providing a database containing the parameters of all models in a full model-space. For test data a publicly available fMRI dataset of 60 subjects was used. First, we reimplemented the deterministic bilinear DCM algorithm in the ReDCM R package, increasing computational speed during model estimation. Then, three network search algorithms have been adapted for DCM, and we demonstrated how modifications to these methods, based on DCM posterior parameter estimates, can enhance search performance. Comparison of the results are based on model evidence, structural similarities and the number of model estimations needed during search. An analytical approach using Bayesian model reduction (BMR) for efficient network discovery is already available for DCM. Comparing model search methods we found that topological algorithms often outperform analytical methods for single-subject analysis and achieve similar results for recovering common network properties of the winning model family, or set of models, obtained by multi-subject family-wise analysis. However, network search methods show their limitations in higher level statistical analysis of parametric empirical Bayes. Optimizing such linear modeling schemes the BMR methods are still considered the recommended approach. We envision the freely available database of estimated model-spaces to help further studies of the DCM model-space, and the ReDCM package to be a useful contribution for Bayesian inference within and beyond the field of neuroscience.