Immune landscape of the enteric nervous system differentiates Parkinson's disease patients from controls: The PADUA-CESNE cohort.

BACKGROUND: Gastrointestinal dysfunction has emerged as a prominent early feature of Parkinson's Disease, shedding new light on the pivotal role of the enteric nervous system in its pathophysiology. However, the role of immune-cell clusters and inflammatory and glial markers in the gut pathogenetic process needs further elucidation. OBJECTIVES: We aimed to study duodenum tissue samples to characterize PD's enteric nervous system pathology further. Twenty patients with advanced PD, six with early PD, and 18 matched controls were included in the PADUA-CESNE cohort. METHODS: Duodenal biopsies from 26 patients with early to advanced stage PD and 18 age-matched HCs were evaluated for the presence of surface markers (CD3+, CD4+, CD8+, CD20+, CD68+, HLA-DR), presence of misfolded alpha-synuclein and enteric glial alteration (GFAP). Correlation of immulogic pattern and clinical characteristic were analyzed. RESULTS: The findings validate that in patients with Parkinson's Disease, the activation and reactive gliosis are linked to the neurodegeneration triggered by the presence of misfolded alpha-synuclein in the enteric nervous system. This process intensifies from the initial to the advanced stages of the disease. The clusters of T- and B-lymphocytes in the enteric system, along with the overall expression of HLA-DR in antigen-presenting cells, exceeded those in the control group. Conversely, no differences in terms of macrophage populations were found. CONCLUSIONS: These findings broaden our understanding of the mechanisms underlying the enteric nervous system's involvement in PD and point to the gastrointestinal system as a potential therapeutic target, especially in the early stages of the disease. Moreover, our results propose a role of T- and B-lymphocytes in maintaining inflammation and ultimately influencing alpha-synuclein misfolding and aggregation.

Myofascial junction: Emerging insights into the connection between deep/muscular fascia and muscle.

Muscles and fasciae are mutually connected and are influenced by force transmission. However, the anatomical connectivity and histological features of these structures remain unclear. The aim of this study was to assess the evidence for connection between muscles and deep/muscular fasciae. We assessed this relationship in different topographical regions of human cadavers and in mice. The results showed that myofascial junctions (MFJ) were made up of collagen I immune-positive structures occupying an average area of 5.11 ± 0.81 µm2, distributed in discrete regions at the interface between muscle and fascia with an average density of 9.7 ± 2.51 MFJ/mm and an average inclination angle of 35.25 ± 1.52°. These specialized structures also showed collagen III and HA immunopositivity and the presence of elastic fibers. The human myofascial junction can be visualized, opening emerging insights into the connection between deep/muscular fascia and muscle.

Ultrasound Imaging of Thoracolumbar Fascia: A Systematic Review.

Over the past decade, there has been a notable increase in research focused on ultrasound imaging of thoracolumbar fascia (TLF). Nevertheless, published papers' results about the application of US imaging in TLF examination are still sparse. Background and Objevtives: Hence, this systematic review was performed aiming to firstly investigate the use and the methodology of ultrasound imaging to assess pathologic and healthy TLF. Secondarily, we aim to assess intra- and inter-observer reproducibility of US imaging in TLF assessment. Materials and Methods: The search was done on PubMed and Web of Science database from inception to April 2024. Furthermore, the references of included papers were thoroughly checked to find eligible publications. The MeSH keywords used were: "Thoracolumbar fascia", "Ultrasound Imaging", "Ultrasound", "Ultrasonography", and "Ultrasound examination". Results: Studies were aimed primarily at TLF diagnosis, treatment monitoring, or evaluating movement-related changes, underscoring the diverse clinical applications. The US parameters assessed included TLF thickness, echogenicity, stiffness, deformation, shear strain, and displacement, providing comprehensive insights into TLF features. Conclusions: Advanced US imaging holds promise as a reliable tool in musculoskeletal assessment, offering insights into TLF pathology/disfunction, treatment outcomes, and movement dynamics.

A Self-Similarity Logic May Shape the Organization of the Nervous System.

From the morphological point of view, the nervous system exhibits a fractal, self-similar geometry at various levels of observations, from single cells up to cell networks. From the functional point of view, it is characterized by a hierarchical organization in which self-similar structures (networks) of different miniaturizations are nested within each other. In particular, neuronal networks, interconnected to form neuronal systems, are formed by neurons, which operate thanks to their molecular networks, mainly having proteins as components that via protein-protein interactions can be assembled in multimeric complexes working as micro-devices. On this basis, the term "self-similarity logic" was introduced to describe a nested organization where, at the various levels, almost the same rules (logic) to perform operations are used. Self-similarity and self-similarity logic both appear to be intimately linked to the biophysical evidence for the nervous system being a pattern-forming system that can flexibly switch from one coherent state to another. Thus, they can represent the key concepts to describe its complexity and its concerted, holistic behavior.

Optimizing healthcare in space: the role of ultrasound imaging in medical conditions.

In the context of long-distance space travel, managing medical conditions presents unique challenges due to communication delays. Consequently, onboard physicians must possess proficiency in diagnostic tools such as ultrasound, which has demonstrated its efficacy in the Space. However, there is a notable lack of comprehensive discussion regarding its effectiveness in handling medical scenarios in the Space. This bibliometric and systematic review aims to provide an updated analysis of the evidence supporting the role of ultrasound imaging in diagnosing medical conditions within microgravity environments.

Ultrasound Imaging in Football Players with Previous Multiple Ankle Sprains: Keeping a Close Eye on Superior Ankle Retinaculum.

The superior extensor ankle retinaculum (SEAR), a transversely fascial thickening positioned above the tibia-talar joint, serves as a crucial anatomical structure in ankle stability. The purpose of this study was to measure and compare by ultrasound (US) imaging the bilateral thickness and echogenicity of SEAR in football players with previous multiple ankle sprains (group 1) and healthy volunteers (group 2). A cross-sectional study was performed using ultrasound imaging to measure longitudinal and transversal axes using a new protocol in a sample of 50 subjects: 25 football players with previous multiple ankle sprains and 25 healthy subjects. The findings for SEAR thickness revealed statistically significant differences for both axes (p = 0.0011 and p = 0.0032) between the healthy side and the previously sprained side, and with the corresponding side of group 2 (p = 0.003 and p = 0.004). Moreover, in group 1, regarding the ROI echogenicity, a statistically significant difference was found between the sides (p = 0.0378). These findings suggest that the football players with previous ankle sprains showed a thicker and inhomogeneous SEAR on the sprain side, unveiling a remodeling of this structure compared to the other side and to the healthy volunteers. In these athletes, during US examination, one needs to keep "a US eye" on side-to-side SEAR comparisons.

Carotid body plastic behavior: evidence for D2-H3 receptor-receptor interactions.

Dopamine and histamine receptors D2R and H3R are G protein-coupled receptors (GPCRs) which can establish physical receptor-receptor interactions (RRIs), leading to homo/hetero-complexes in a dynamic equilibrium. Although D2R and H3R expression has been detected within the carotid body (CB), their possible heterodimerization has never been demonstrated. The aim of this work was to verify D2R and H3R colocalization in the CB, thus suggesting a possible interplay that, in turn, may be responsible of specific D2R-H3R antagonistic functional implications. The CBs of both Sprague-Dawley rats (n = 5) and human donors (n = 5) were dissected, and immunolocalization of D2R and H3R was performed; thereafter, in situ proximity ligation assay (PLA) was developed. According to experimental evidence (immunohistochemistry and double immunofluorescence), all the samples displayed positive D2R/H3R elements; hence, PLA assay followed by confocal microscopy analysis was positive for D2R-H3R RRIs. Additionally, D2R-H3R heterodimers were mainly detected in type I cells (ßIII-tubulin-positive cells), but type II cells' involvement cannot be excluded. RRIs may play a role in functional modulation of CB cells; investigating RRIs in the CB may guide toward the comprehension of its plastic changes and fine regulatory role while also unveiling their possible clinical implications.