Polymers with functionalized surfaces have attracted a lot of attention in the last few years. Due to the progress in the techniques of polymer micro-patterning, miniaturized bioanalytical assays and biocompatible devices can be developed. In the presented work, we performed surface modification of polyethylene naphthalate (PEN) foil by an excimer laser beam through a photolithographic contact mask. The aim was to fabricate micro-patterned areas with surface functional groups available for localized covalent immobilization of biotin. It was found out that depending on the properties of the laser scans, a polymer surface exhibits different degrees of modification and as a consequence, different degrees of surface biotinylation can be achieved. Several affinity tests with optical detection of fluorescently labeled streptavidin were successfully performed on biotinylated micro-patterns of a PEN foil. The polymer surface properties were also evaluated by electrokinetic analysis, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The results have shown that PEN foils can be considered suitable substrates for construction of micro-patterned bioanalytical affinity assays.
- MeSH
- Biotin chemistry MeSH
- Biotinylation MeSH
- Photochemical Processes MeSH
- Lab-On-A-Chip Devices MeSH
- Lasers, Excimer MeSH
- Microtechnology MeSH
- Naphthalenes chemistry radiation effects MeSH
- Polyethylenes chemistry radiation effects MeSH
- Surface Properties MeSH
- Streptavidin chemistry MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Hepatic in vitro models that accurately replicate phenotypes and functionality of the human liver are needed for applications in toxicology, pharmacology and biomedicine. Notably, it has become clear that liver function can only be sustained in 3D culture systems at physiologically relevant cell densities. Additionally, drug metabolism and drug-induced cellular toxicity often follow distinct spatial micropatterns of the metabolic zones in the liver acinus, calling for models that capture this zonation. We demonstrate the manufacture of accurate liver microphysiological systems (MPS) via engineering of 3D stereolithography printed hydrogel chips with arrays of diffusion open synthetic vasculature channels at spacings approaching in vivo capillary distances. Chip designs are compatible with seeding of cell suspensions or preformed liver cell spheroids. Importantly, primary human hepatocytes (PHH) and hiPSC-derived hepatocyte-like cells remain viable, exhibit improved molecular phenotypes compared to isogenic monolayer and static spheroid cultures and form interconnected tissue structures over the course of multiple weeks in perfused culture. 3D optical oxygen mapping of embedded sensor beads shows that the liver MPS recapitulates oxygen gradients found in the acini, which translates into zone-specific acet-ami-no-phen toxicity patterns. Zonation, here naturally generated by high cell densities and associated oxygen and nutrient utilization along the flow path, is also documented by spatial proteomics showing increased concentration of periportal- versus perivenous-associated proteins at the inlet region and vice versa at the outlet region. The presented microperfused liver MPS provides a promising platform for the mesoscale culture of human liver cells at phenotypically relevant densities and oxygen exposures. STATEMENT OF SIGNIFICANCE: A full 3D tissue culture platform is presented, enabled by massively parallel arrays of high-resolution 3D printed microperfusion hydrogel channels that functionally mimics tissue vasculature. The platform supports long-term culture of liver models with dimensions of several millimeters at physiologically relevant cell densities, which is difficult to achieve with other methods. Human liver models are generated from seeded primary human hepatocytes (PHHs) cultured for two weeks, and from seeded spheroids of hiPSC-derived human liver-like cells cultured for two months. Both model types show improved functionality over state-of-the-art 3D spheroid suspensions cultured in parallel. The platform can generate physiologically relevant oxygen gradients driven by consumption rather than supply, which was validated by visualization of embedded oxygen-sensitive microbeads, which is exploited to demonstrate zonation-specific toxicity in PHH liver models.
- MeSH
- Hepatocytes * metabolism MeSH
- Hydrogels metabolism MeSH
- Liver * MeSH
- Oxygen metabolism MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The existence of pattern recognition receptors (PRRs) on immune cells was discussed in 1989 by Charles Janeway, Jr., who proposed a general concept of the ability of PRRs to recognize and bind conserved molecular structures of microorganisms known as pathogen-associated molecular patterns (PAMPs). Upon PAMP engagement, PRRs trigger intracellular signaling cascades resulting in the expression of various proinflammatory molecules. These recognition molecules represent an important and efficient innate immunity tool of all organisms. As invertebrates lack the instruments of the adaptive immune system, based on "true" lymphocytes and functional antibodies, the importance of PRRs are even more fundamental. In the present review, the structure, specificity, and expression profiles of PRRs characterized in annelids are discussed, and their role in innate defense is suggested.
- MeSH
- Annelida immunology MeSH
- Membrane Glycoproteins chemistry genetics metabolism MeSH
- Pathogen-Associated Molecular Pattern Molecules immunology metabolism MeSH
- Immunity, Innate * MeSH
- Acute-Phase Proteins chemistry genetics metabolism MeSH
- Receptors, Pattern Recognition chemistry genetics metabolism MeSH
- Gene Expression Regulation MeSH
- Signal Transduction immunology MeSH
- Tissue Distribution MeSH
- Toll-Like Receptors chemistry genetics metabolism MeSH
- Carrier Proteins chemistry genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Implantable sensor devices require coatings that efficiently interface with the tissue environment to mediate biochemical analysis. In this regard, bioinspired polymer hydrogels offer an attractive and abundant source of coating materials. However, upon implantation these materials generally elicit inflammation and the foreign body reaction as a consequence of protein fouling on their surface and concomitant poor hemocompatibility. In this report we investigate a strategy to endow chitosan hydrogel coatings with antifouling properties by the grafting of polymer brushes in a "grafting-from" approach. Chitosan coatings were functionalized with polymer brushes of oligo(ethylene glycol) methyl ether methacrylate and 2-hydroxyethyl methacrylate using photoinduced single electron transfer living radical polymerization and the surfaces were thoroughly characterized by XPS, AFM, water contact angle goniometry, and in situ ellipsometry. The antifouling properties of these new bioinspired hydrogel-brush coatings were investigated by surface plasmon resonance. The influence of the modifications to the chitosan on hemocompatibility was assessed by contacting the surfaces with platelets and leukocytes. The coatings were hydrophilic and reached a thickness of up to 180 nm within 30 min of polymerization. The functionalization of the surface with polymer brushes significantly reduced the protein fouling and eliminated platelet activation and leukocyte adhesion. This methodology offers a facile route to functionalizing implantable sensor systems with antifouling coatings that improve hemocompatibility and pave the way for enhanced device integration in tissue.
- MeSH
- Platelet Activation drug effects MeSH
- Coated Materials, Biocompatible chemistry pharmacology MeSH
- Biosensing Techniques methods MeSH
- Cell Adhesion drug effects MeSH
- Chitosan chemistry MeSH
- Hydrogels chemistry pharmacology MeSH
- Infusion Pumps, Implantable MeSH
- Leukocytes cytology drug effects MeSH
- Humans MeSH
- Methacrylates chemistry MeSH
- Polyethylene Glycols chemistry MeSH
- Polymerization MeSH
- Primary Cell Culture MeSH
- Blood Platelets drug effects MeSH
- Free Radicals MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Spatial and temporal resolution of brain network activity can be improved by combining different modalities. Functional Magnetic Resonance Imaging (fMRI) provides full brain coverage with limited temporal resolution, while electroencephalography (EEG), estimates cortical activity with high temporal resolution. Combining them may provide improved network characterization. NEW METHOD: We examined relationships between EEG spatiospectral pattern timecourses and concurrent fMRI BOLD signals using canonical hemodynamic response function (HRF) with its 1st and 2nd temporal derivatives in voxel-wise general linear models (GLM). HRF shapes were derived from EEG-fMRI time courses during "resting-state", visual oddball and semantic decision paradigms. RESULTS: The resulting GLM F-maps self-organized into several different large-scale brain networks (LSBNs) often with different timing between EEG and fMRI revealed through differences in GLM-derived HRF shapes (e.g., with a lower time to peak than the canonical HRF). We demonstrate that some EEG spatiospectral patterns (related to concurrent fMRI) are weakly task-modulated. COMPARISON WITH EXISTING METHOD(S): Previously, we demonstrated 14 independent EEG spatiospectral patterns within this EEG dataset, stable across the resting-state, visual oddball and semantic decision paradigms. Here, we demonstrate that their time courses are significantly correlated with fMRI dynamics organized into LSBN structures. EEG-fMRI derived HRF peak appears earlier than the canonical HRF peak, which suggests limitations when assuming a canonical HRF shape in EEG-fMRI. CONCLUSIONS: This is the first study examining EEG-fMRI relationships among independent EEG spatiospectral patterns over different paradigms. The findings highlight the importance of considering different HRF shapes when spatiotemporally characterizing brain networks using EEG and fMRI.
- MeSH
- Adult MeSH
- Electroencephalography methods MeSH
- Functional Neuroimaging methods MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Young Adult MeSH
- Nerve Net diagnostic imaging physiology MeSH
- Neurovascular Coupling physiology MeSH
- Psycholinguistics MeSH
- Cerebrum diagnostic imaging physiology MeSH
- Visual Perception physiology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
INTRODUCTION AND HYPOTHESIS: Members of the International Urogynecological Association (IUGA) come from different geographic locations and practice settings. A member survey regarding practice patterns provides valuable information for practitioners and researchers alike, and allows the IUGA to discover areas to focus on education and information dissemination. METHODS: A questionnaire was developed by the IUGA Research and Development committee and distributed electronically to IUGA surgeons. Answers were analyzed in reference to demographics, geographic distribution, and academic affiliation. RESULTS: Five hundred sixty-four members answered the questionnaire, representing a 28 % response rate, and closely reflecting the geographic distribution of IUGA membership. Preferred surgical treatment for uncomplicated SUI was the mid-urethral trans-obturator sling (49.7 %). Vaginal mesh was mainly used for repair of recurrent POP (20.4 %). Pessary use was offered "always" or "frequently" by 61.5 %, with no difference in academic affiliation, but significant differences based on region of practice. Compared to practitioners in non-academic centers, those with academic affiliation utilized Urodynamic studies (UDS) and Magnetic Resonance Imaging (MRI) more frequently in the evaluation of POP. Regions of practice significantly influenced the majority of practice patterns, with the highest impact found in the use of robotic assistance. CONCLUSIONS: Many practice patterns in the evaluation and treatment of POP and SUI depend on academic affiliation and geographic location. Practice patterns are not always based on most recent evidence-based data.
- MeSH
- Surgical Mesh utilization MeSH
- Adult MeSH
- Gynecology statistics & numerical data MeSH
- Internationality MeSH
- Practice Patterns, Physicians' statistics & numerical data MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging utilization MeSH
- Young Adult MeSH
- Pessaries utilization MeSH
- Pelvic Organ Prolapse surgery MeSH
- Surveys and Questionnaires MeSH
- Urinary Incontinence, Stress surgery MeSH
- Suburethral Slings utilization MeSH
- Ultrasonography utilization MeSH
- Urology statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The microvascular pattern in the histological section, i.e. the point-pattern composed of capillaries perpendicular to the plane of section, contains information about the three-dimensional structure of the capillary network. Histological processing is followed by the shrinkage of tissue of uncertain magnitude. In order to obtain relevant information, the scale-independent analysis is necessary. We used an approach based on the Minkowski cover of measured set. The true fractal dimension of the point pattern is obviously of zero, but the artificial result of the algorithm can be related to the complexity of shape. We fitted the log-log plot by the modified rounded ramp function and the slope of the oblique part was used as the fractal based descriptor. We demonstrated on histological samples of the heart that this fractal-based parameter has the property of scale and rotation invariance.
The microvascular pattern in the histological section, i.e. the point-pattern composed of capillaries perpendicular to the plane of section, contains information about the three-dimensional structure of the capillary network. Histological processing is followed by the shrinkage of tissue of uncertain magnitude. In order to obtain relevant information, the scale-independent analysis is necessary. We used an approach based on the Minkowski cover of measured set. The true fractal dimension of the point pattern is obviously of zero, but the artificial result of the algorithm can be related to the complexity of shape. We fitted the log-log plot by the modified rounded ramp function and the slope of the oblique part was used as the fractal based descriptor. We demonstrated on histological samples of the heart that this fractal-based parameter has the property of scale and rotation invariance.
- MeSH
- Fractals MeSH
- Histological Techniques * MeSH
- Image Interpretation, Computer-Assisted * MeSH
- Humans MeSH
- Pattern Recognition, Automated MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Patients with bipolar disorder (BD) and major depressive disorder (MDD) exhibit depressive episodes with similar symptoms despite having different and poorly understood underlying neurobiology, often leading to misdiagnosis and improper treatment. This exploratory study examined whole-brain functional connectivity (FC) using FC multivariate pattern analysis (fc-MVPA) to identify the FC patterns with the greatest ability to distinguish between currently depressed patients with BD type I (BD I) and those with MDD. METHODOLOGY: In a cross-sectional design, 41 BD I, 40 MDD patients and 63 control participants completed resting state functional magnetic resonance imaging scans. Data-driven fc-MVPA, as implemented in the CONN toolbox, was used to identify clusters with differential FC patterns between BD patients and MDD patients. The identified cluster was used as a seed in a post hoc seed-based analysis (SBA) to reveal associated connectivity patterns, followed by a secondary ROI-to-ROI analysis to characterize differences in connectivity between these patterns among BD I patients, MDD patients and controls. RESULTS: FC-MVPA identified one cluster located in the right frontal pole (RFP). The subsequent SBA revealed greater FC between the RFP and posterior cingulate cortex (PCC) and between the RFP and the left inferior/middle temporal gyrus (LI/MTG) and lower FC between the RFP and the left precentral gyrus (LPCG), left lingual gyrus/occipital cortex (LLG/OCC) and right occipital cortex (ROCC) in MDD patients than in BD patients. Compared with the controls, ROI-to-ROI analysis revealed lower FC between the RFP and the PCC and greater FC between the RFP and the LPCG, LLG/OCC and ROCC in BD patients; in MDD patients, the analysis revealed lower FC between the RFP and the LLG/OCC and ROCC and greater FC between the RFP and the LI/MTG. CONCLUSIONS: Differences in the RFP FC patterns between currently depressed patients with BD and those with MDD suggest potential neuroimaging markers that should be further examined. Specifically, BD patients exhibit increased FC between the RFP and the motor and visual networks, which is associated with psychomotor symptoms and heightened compensatory frontoparietal FC to counter distractibility. In contrast, MDD patients exhibit increased FC between the RFP and the default mode network, corresponding to sustained self-focus and rumination.
- MeSH
- Bipolar Disorder * physiopathology diagnostic imaging MeSH
- Depressive Disorder, Major * physiopathology diagnostic imaging MeSH
- Adult MeSH
- Connectome methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * methods MeSH
- Brain Mapping methods MeSH
- Brain physiopathology diagnostic imaging MeSH
- Multivariate Analysis MeSH
- Nerve Net diagnostic imaging physiopathology MeSH
- Neural Pathways physiopathology diagnostic imaging MeSH
- Cross-Sectional Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Různé vyšetřovací modality magnetické rezonance (MR) prokázaly v mnoha publikovaných studiích morfologické i funkční změny v mozkové tkáni u osob se schizofrenií (SZ). Volumetrickými metodami byly popsány atrofické změny některých oblastí šedé hmoty, pomocí metody zobrazení difuzního tenzoru především pokles hodnot frakční anizotropie bílé hmoty. Tyto změny jsou obecně mírného stupně, široké distribuce a v čase pravděpodobně progredují. Při resting-state funkční magnetické rezonanci byly opakovaně nalezeny významné změny konektivity jednotlivých funkčních center mozku. Vesměs jsou MR nálezy kompatibilní s upřednostňovanou teorií o poruše konektivity mozku u schizofrenie. Mezi výsledky dosud publikovaných studií panuje ovšem velmi značná variabilita, která má více příčin. K těm nejvýznamnějším řadíme nejednotnost v metodice prováděných studií, metodologické a technické limitace MR, malé počty subjektů ve většině publikovaných studií, výraznou heterogenitu psychických a potažmo strukturálních změn u nemocných se schizofrenií, dobu trvání manifestního onemocnění (první ataka versus chronické stadium), možný vliv medikace, toxických a návykových látek na strukturální a funkční změny mozku atd. Má-li magnetická rezonance najít pevné klinické uplatnění v diagnostice schizofrenie, bude potřeba rozsáhlých multicentrických studií s klinicky homogenními skupinami probandů a jednotnou metodikou. V článku jsou shrnuty dosavadní znalosti o strukturálních a funkčních změnách mozku u schizofrenie.
Structural and functional cerebral changes in subjects suffering from schizophrenia (SZ) were proven by means of several modalities of magnetic resonance imaging (MRI) according to the results of numerous studies. Atrophic changes were reported by using volumetric methods, microstructural changes of white matter were described by diffusion tensor imaging. These changes are of mild degree yet likely of widespread distribution and progressing over time. Extensive changes of connectivity were observed by resting-state functional MRI. MRI findings are generally compatible with currently preferred hypothesis of cerebral dysconnectivity in SZ. The published results show considerable degree of variability which can be explained by many reasons. Those of the highest importance are: different methodology, technical MRI limitations, low number of subjects included, high heterogeneity and variability of symptoms of the disease, variable duration of symptoms (first episode versus chronic illness), effects of medication, abuse of toxic substances etc. Before MRI can be utilized for diagnosing SZ in the clinical settings, more comprehensive multi-centric studies of homogenous cohorts with unified methodology are needed. In this review, we summarize the current knowledge of structural and functional cerebral changes in schizophrenia.
- MeSH
- Chronic Disease MeSH
- Clinical Studies as Topic MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Meta-Analysis as Topic MeSH
- Brain * physiopathology MeSH
- Neuroimaging * methods MeSH
- Pattern Recognition, Automated MeSH
- Schizophrenia * diagnosis physiopathology MeSH
- Gray Matter physiopathology MeSH
- Diffusion Tensor Imaging methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
OBJECTIVE: Growing interest in the examination of large-scale brain network functional connectivity dynamics is accompanied by an effort to find the electrophysiological correlates. The commonly used constraints applied to spatial and spectral domains during electroencephalogram (EEG) data analysis may leave part of the neural activity unrecognized. We propose an approach that blindly reveals multimodal EEG spectral patterns that are related to the dynamics of the BOLD functional network connectivity. APPROACH: The blind decomposition of EEG spectrogram by parallel factor analysis has been shown to be a useful technique for uncovering patterns of neural activity. The simultaneously acquired BOLD fMRI data were decomposed by independent component analysis. Dynamic functional connectivity was computed on the component's time series using a sliding window correlation, and between-network connectivity states were then defined based on the values of the correlation coefficients. ANOVA tests were performed to assess the relationships between the dynamics of between-network connectivity states and the fluctuations of EEG spectral patterns. MAIN RESULTS: We found three patterns related to the dynamics of between-network connectivity states. The first pattern has dominant peaks in the alpha, beta, and gamma bands and is related to the dynamics between the auditory, sensorimotor, and attentional networks. The second pattern, with dominant peaks in the theta and low alpha bands, is related to the visual and default mode network. The third pattern, also with peaks in the theta and low alpha bands, is related to the auditory and frontal network. SIGNIFICANCE: Our previous findings revealed a relationship between EEG spectral pattern fluctuations and the hemodynamics of large-scale brain networks. In this study, we suggest that the relationship also exists at the level of functional connectivity dynamics among large-scale brain networks when no standard spatial and spectral constraints are applied on the EEG data.
- MeSH
- Time Factors MeSH
- Adult MeSH
- Electroencephalography methods MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Young Adult MeSH
- Brain diagnostic imaging physiology MeSH
- Nerve Net diagnostic imaging physiology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH