Commentary: Prestimulus theta oscillations and connectivity modulate pain perception

Pain experience includes the fine-grain integration of both attentive and automatic (bottom-up; Legrain et al., 2012), as well as affective and intentional (top-down; Buschman and Miller, 2007) processes. While the neural underpinnings of post-stimulus pain processing have been deeply explored (Hauck et al., 2008), the oscillatory brain activity preceding pain processing is less far investigated

Learning-based Framework for US Signals Super-resolution

We propose a novel deep-learning framework for super-resolution ultrasound images and videos in terms of spatial resolution and line reconstruction. We up-sample the acquired low-resolution image through a vision-based interpolation method; then, we train a learning-based model to improve the quality of the up-sampling. We qualitatively and quantitatively test our model on different anatomical districts (e.g., cardiac, obstetric) images and with different up-sampling resolutions (i.e., 2X, 4X). Our method improves the PSNR median value with respect to SOTA methods of $1.7\%$ on obstetric 2X raw images, $6.1\%$ on cardiac 2X raw images, and $4.4\%$ on abdominal raw 4X images; it also improves the number of pixels with a low prediction error of $9.0\%$ on obstetric 4X raw images, $5.2\%$ on cardiac 4X raw images, and $6.2\%$ on abdominal 4X raw images. The proposed method is then applied to the spatial super-resolution of 2D videos, by optimising the sampling of lines acquired by the probe in terms of the acquisition frequency. Our method specialises trained networks to predict the high-resolution target through the design of the network architecture and the loss function, taking into account the anatomical district and the up-sampling factor and exploiting a large ultrasound data set. The use of deep learning on large data sets overcomes the limitations of vision-based algorithms that are general and do not encode the characteristics of the data. Furthermore, the data set can be enriched with images selected by medical experts to further specialise the individual networks. Through learning and high-performance computing, our super-resolution is specialised to different anatomical districts by training multiple networks. Furthermore, the computational demand is shifted to centralised hardware resources with a real-time execution of the network's prediction on local devices

Deconvolution increases the accuracy of measurements by image analysis in a model of trimethyltin-induced reactive gliosis of the rat entorhinal cortex

Digital images were used in applications such as astronomy, medicine, physics and biology, to record and analyze results from experiments Due to the features of the imaging system, the recorded images can be degraded by blurring and noise. Image deconvolution, or image deblurring, is the process of reconstructing or estimating the true image from the degraded one [1]. In order to optimize morphometrical analysis of Glial Fibrillary Acidic protein (GFAp)-immunoreactive astrocyte of the whole rat entorhinal cortex of both trimethyltin hydrochloride- and saline treated rats, large images of it (about 30 000 x 20 000 pixels) were digitized by a microscope with a X – Y motorized computer-managed stage and an autofocusing system, using an objective 40x, a digital camera 2560x1920 RGB. Moreover it has been optimized a procedure of deconvolution and segmentation under the NIH ImageJ system. Such large images were first deblurred, by Modified Residual Norm Steepest Descent (MRNSD) and Wiener Filter Preconditioned Landweber (WPL) algoritms, and segmented, then analyzed, to measure the % of the area (in µm2) occupied by GFAp-immunoreactive cell bodies and processes, and classical morphometrical parameters. Statistical analysis was performed to describe obtained data and to point out differences between segmented only versus deblurred-segmented images. Our results can be summarized as follows. 1. Large images can be an useful tool to identify precisely the distribution of reactive astrocytes in the rat entorhinal cortex. 2. Deconvolution avoid an overestimation of the area of immunoreative astrocytes of about 10-15%. Segmentation allow a measurement with improved accuracy, precision and uncertainty. 3. This approach is time consuming and requires a multi-core hardware with a large amount of available RAM

Uterine fibroid pseudocapsule studied by transmission electronmicroscopy.

OBJECTIVE: The fibroid pseudocapsule is a structure which surrounds the uterine fibroid, separates it from the uterine tissue and contains a vascular network rich in neurotransmitters like a neurovascular bundle. The authors examined the composition of the fibroid pseudocapsule using electron microscopy. STUDY DESIGN: Twenty non-pregnant patients were submitted to laparoscopic myomectomy by the intracapsular method and samples of the removed pseudocapsules were analyzed using transmission electron microscopy. RESULTS: At the ultrastructural level the pseudocapsule cells have the features of smooth muscle cells similar to the myometrium. So, the pseudocapsules are part of the myometrium which compresses the leiomyoma. CONCLUSION: This ultrastructural feature suggests that when removing fibroids their pseudocapsules should be preserved. This study confirms preliminary evidence that pseudocapsules contain neuropeptides together with their related fibers, as a neurovascular bundle. The surgeon's behavior should be directed to carefully control and spare this muscular surrounding tissue during fibroid excision, in order to preserve the myometrium as much as possible

Biomechanical and proteomic analysis of INF- β-treated astrocytes

Astrocytes have a key role in the pathogenesis of several diseases including multiple sclerosis and were proposed as the designed target for immunotherapy. In this study we used atomic force microscopy (AFM) and proteomics methods to analyse and correlate the modifications induced in the viscoleastic properties of astrocytes to the changes induced in protein expression after interferon- beta (IFN-beta) treatment. Our results indicated that IFN-beta treatment resulted in a significant decrease in the Young's modulus, a measure of cell elasticity, in comparison with control cells. The molecular mechanisms that trigger these changes were investigated by 2DE (two-dimensional electrophoresis) and confocal analyses and confirmed by western blotting. Altered proteins were found to be involved in cytoskeleton organization and other important physiological processes

Formyl Peptide Receptor (FPR)1 Modulation by Resveratrol in an LPS-Induced Neuroinflammatory Animal Model

Among therapeutic approaches that have been investigated, targeting of receptors implicated in managing neuroinflammation has been described. One such family of receptors comprises the formyl peptide receptors (FPRs) whose ligands could play a role in host defense. The murine FPR gene family includes at least six members while in humans there are only three. The two most important members are the Fpr1 and Fpr2. Fpr1encodes murine FPR1, which is considered the murine orthologue of human FPR. Resveratrol, a non-flavonoid polyphenol rich in red wine and grapes, apart from its beneficial health effects and anti-inflammatory properties, has been reported to reduce neuroinflammation in different neurodegenerative disease models. Resveratrol anti-inflammatory responses involve the activation of the protein deacetylase sirtuin 1 (SIRT1) gene. In this work we have investigated in an LPS-based murine model of neuroinflammation the role of FPR1, examining not only if this receptor undergoes a reduction of its expression during neuroinflammation, but also whether treatment with resveratrol was able to modulate its expression leading to an amelioration of neuroinflammatory picture in a murine model of neuroinflammation. Results of this work showed that FPR1 together with SIRT1 resulted upregulated by resveratrol treatment and that this increase is associated with an amelioration of the neuroinflammatory picture, as demonstrated by the induction of IL-10 and IL1-RA expression and the downregulation of proinflammatory mediators, such as TNF-α and IL-1β. The expression and the modulation of FPR1 by resveratrol may be evaluated in order to propose a novel anti-inflammatory and pro-resolving therapeutic approach for the reduction of the detrimental effects associated with neuro-inflammation based neurodegenerative diseases and also as a promising strategy to promote human health by a diet rich in antioxidative bioactive compounds

Potential Role of OERP as Early Marker of Mild Cognitive Impairment

Olfactory impairment is present in up to 90% of patients with Alzheimer’s disease (AD) and is present in certain cases of mild cognitive impairment (MCI), a transient phase between normal aging and dementia. Subjects affected by MCI have a higher risk of developing dementia compared to the general population, and studies have found that olfactory deficits could be an indicator of whether such a conversion might happen. Following these assumptions, aim of this study was to investigate olfactory perception in MCI patients. We recruited 12 MCI subjects (mean age 70 ± 6.7 years) through the Alzheimer Assessment Unit (UVA Unite) of ASL Lecce (Italy), and 12 healthy geriatric volunteers (HS) as the control group (mean age 64 ± 6.0 years), all of whom were first evaluated via a panel of neuropsychological tests. Subjects were asked to perform an olfactory recognition task involving two scents: rose and eucalyptus, administrated in the context of an oddball task during EEG recordings. Olfactory event-related potential (OERP) components N1 and Late Positive Potential (LPC) were then analyzed as measures of the sensorial and perceptive aspects of the olfactory response, respectively. It was determined that, in the MCI group, both the N1 and LPC components were significantly different compared to those of the HS group during the execution of the oddball task. In particular, the N1 amplitude, was reduced, while the LPC amplitude was increased, indicating that a degree of perceptive compensation can occur when sensorial function is impaired. Further, a correlation analysis, involving OERP components and neuropsychological battery scores, indicated that impairment of olfactory perception may share common pathways with impairments of the spatial system and long-term memory processing

Inflammatory Response Modulation by Vitamin C in an MPTP Mouse Model of Parkinson's Disease

Vitamin C (Vit C) is anutrient present in many foods, particularly citrus fruits, green vegetables, tomatoes, and potatoes. Vit C is studied for its applications in the prevention and management of different pathologies, including neurodegenerative diseases. Neuroinflammation is a defense mechanism activated by a stimulus or an insult that is aimed at the preservation of the brain by promoting tissue repair and removing cellular debris; however, persistent inflammatory responses are detrimental and may lead to the pathogenesis and progression of neurodegenerative diseases like Parkinson's disease (PD) and Alzheimer's disease. PD is one of the most common chronic progressive neurodegenerative disorders, and oxidative stress is one of the most important factors involved in its pathogenesis and progression.Due to this, research on antioxidant and anti-inflammatory compounds is an important target for counteracting neurodegenerative diseases, including PD. In the central nervous system, the presence of Vit C in the brain is higher than in other body districts, but why and how this occurs is still unknown. In this research, Vit C, with its anti-inflammatory and anti-oxidative properties, is studied to better understand its contribution to brain protection; in particular, we have investigated the neuroprotective effects of Vit C in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of PD and its role in the modulation of neuroinflammation. First, we observed that Vit C significantly decreased the MPTP-induced loss of tyrosine hydroxylase (TH)-positive dopaminergic neuronal cells in the substantia nigra, as well as microglial cell activation and astrogliosis. Furthermore, gait and spontaneous locomotor activity, evaluated by an automated treadmill and the Open Field test, respectively, were partially ameliorated by Vit C treatment in MPTP-intoxicated animals. In relation to neuroinflammation, results show that Vit C reduced the protein and mRNA expression of inflammatory cytokines such as IL-6, TLR4, TNF-α, iNOS, and CD40, while anti-inflammatory proteins such as IL-10, CD163, TGF-β, and IL-4 increased. Interestingly, we show for the first time that Vit C reduces neuroinflammation by modulating microglial polarization and astrocyte activation. Moreover, Vit C was able to reduce NLRP3 activation, which is linked to the pathogenesis of many inflammatory diseases, including neuroinflammatory disorders. In conclusion, our study provides evidence that Vit C may represent a new promising dietary supplement for the prevention and alleviation of the inflammatory cascade of PD, thus contributing to neuroprotection

Increased hexosamine biosynthetic pathway flux alters cell-cell adhesion in INS-1E cells and murine islets

Purpose In type 2 Diabetes, beta-cell failure is caused by loss of cell mass, mostly by apoptosis, but also by simple dysfunction (dedifferentiation, decline of glucose-stimulated insulin secretion). Apoptosis and dysfunction are caused, at least in part, by glucotoxicity, in which increased flux of glucose in the hexosamine biosynthetic pathway plays a role. In this study, we sought to clarify whether increased hexosamine biosynthetic pathway flux affects another important aspect of beta-cell physiology, that is beta-cell-beta-cell homotypic interactions. Methods We used INS-1E cells and murine islets. The expression and cellular distribution of E-cadherin and beta-catenin was evaluated by immunofluorescence, immunohistochemistry and western blot. Cell-cell adhesion was examined by the hanging-drop aggregation assay, islet architecture by isolation and microscopic observation. Results E-cadherin expression was not changed by increased hexosamine biosynthetic pathway flux, however, there was a decrease of cell surface, and an increase in intracellular E-cadherin. Moreover, intracellular E-cadherin delocalized, at least in part, from the Golgi complex to the endoplasmic reticulum. Beta-catenin was found to parallel the E-cadherin redistribution, showing a dislocation from the plasmamembrane to the cytosol. These changes had as a phenotypic consequence a decreased ability of INS-1E to aggregate. Finally, in ex vivo experiments, glucosamine was able to alter islet structure and to decrease surface abundandance of E-cadherin and beta-catenin. Conclusion Increased hexosamine biosynthetic pathway flux alters E-cadherin cellular localization both in INS-1E cells and murine islets and affects cell-cell adhesion and islet morphology. These changes are likely caused by alterations of E-cadherin function, highlighting a new potential target to counteract the consequences of glucotoxicity on beta-cells