Insoluble polysaccharides produced in plant cell cultures protect from Clostridioides difficile colitis.

Clostridioides difficile infection (CDI) poses a significant health threat due to high recurrence rates. Antimicrobial agents are commonly used to manage CDI-related diarrhoea; however, by aggravating intestinal dysbiosis, antibiotics enable C. difficile spores germination and production of toxins, the main virulence factors. Therefore, the binding of exotoxins using adsorbents represents an attractive alternative medication for the prevention and treatment of relapses. In this study, we provided evidence that the natural insoluble polysaccharides, named ABR119, extracted by plant cell cultures, effectively trap C. difficile toxins. In our experiments, ABR119 exhibited no cytotoxicity in vitro and was safely administered in vivo. In the animal model of C. difficile-associated colitis, ABR119 (50 mg/kg body weight) significantly reduced the colonic myeloperoxidase activity and severity of inflammation, preventing body weight loss. These effects were not evident when we treated animals with wheat bran polysaccharides. We did not detect bacterial killing effects of ABR119 against C. difficile nor against bacterial species of the normal gut microbiota. Moreover, ABR119 did not interfere in vitro with the antimicrobial activities of most clinically used antibiotics. In summary, ABR119 holds promise for treating and preventing C. difficile colitis by trapping the bacterial toxins, warranting further studies to assess the ABR119 potential in human infections caused by C. difficile.

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.

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.

Extracellular Vesicles From Mesenchymal Umbilical Cord Cells Exert Protection Against Oxidative Stress and Fibrosis in a Rat Model of Bronchopulmonary Dysplasia.

Oxidative stress and fibrosis are important stress responses that characterize bronchopulmonary dysplasia (BPD), a disease for which only a therapy but not a cure has been developed. In this work, we investigated the effects of mesenchymal stromal cells-derived extracellular vesicles (MSC-EVs) on lung and brain compartment in an animal model of hyperoxia-induced BPD. Rat pups were intratracheally injected with MSC-EVs produced by human umbilical cord-derived MSC, following the Good Manufacturing Practice-grade (GMP-grade). After evaluating biodistribution of labelled MSC-EVs in rat pups left in normoxia and hyperoxia, oxidative stress and fibrosis investigation were performed. Oxidative stress protection by MSC-EVs treatment was proved both in lung and in brain. The lung epithelial compartment ameliorated glycosaminoglycan and surfactant protein expression in MSC-EVs-injected rat pups compared to untreated animals. Pups under hyperoxia exhibited a fibrotic phenotype in lungs shown by increased collagen deposition and also expression of profibrotic genes. Both parameters were reduced by treatment with MSC-EVs. We established an in vitro model of fibrosis and another of oxidative stress, and we proved that MSC-EVs suppressed the induction of αSMA, influencing collagen deposition and protecting from the oxidative stress. In conclusion, intratracheal administration of clinical-grade MSC-EVs protect from oxidative stress, improves pulmonary epithelial function, and counteracts the development of fibrosis. In the future, MSC-EVs could represent a new cure to prevent the development of BPD.

The suprapatellar fat pad: A histotopographic comparative study.

The suprapatellar fat pad is an adipose tissue located in the anterior knee whose role in osteoarthritis is still debated. Considering that anatomy drives function, the aim of this histotopographic study was to investigate the specific morphological features of the suprapatellar fat pad versus the infrapatellar fat pad in the absence of osteoarthritis, for a broad comparative analysis. Suprapatellar fat pad and infrapatellar fat pad tissue samples (n = 10/group) underwent microscopical/immunohistochemical staining and transmission electron microscopy analysis; thus, tissue-specific characteristics (i.e., vessels and nerve endings presence, lobuli, adipocytes features, septa), including extracellular matrix proteins prevalence (collagens, elastic fibers), were focused. Multiphoton microscopy was also adopted to evaluate collagen fiber orientation within the samples by Fast Fourier Transform (coherency calculation). The absence of inflammation was confirmed, and comparable counted vessels and nerve endings were shown. Like the infrapatellar fat pad, the suprapatellar fat pad appeared as a white adipose tissue with lobuli and septa of comparable diameter and thickness, respectively. Tissue main characteristics were also proved by both semithin sections and transmission electron microscopy analysis. The suprapatellar fat pad adipocytes were roundish and with a smaller area, perimeter, and major axis than that of the infrapatellar fat pad. The collagen fibers surrounding them showed no significant difference in collagen type I and significantly higher values for collagen type III in the infrapatellar fat pad group. Regarding the septa, elastic fiber content was statistically comparable between the two groups, even though more represented by the suprapatellar fat pad. Total collagen was significantly higher in the infrapatellar fat pad and comparing collagen type I and type III they were similarly represented in the whole cohort despite collagen type I appearing to be higher in the infrapatellar fat pad than in the suprapatellar fat pad and vice versa for collagen type III. Second harmonic generation microscopy confirmed through coherency calculation an anisotropic distribution of septa collagen fibers. From a mechanical point of view, the different morphological characteristics determined a major stiffness for the infrapatellar fat pad with respect to the suprapatellar fat pad. This study provides, for the first time, a topographic description of the suprapatellar fat pad compared to the infrapatellar fat pad; differences between the two groups may be attributed to a different anatomical location within the knee; the results gathered here may be useful for a more complete interpretation of osteoarthritis disease, involving not only cartilage but the whole joint.

Brainstem anatomy with 7-T MRI: in vivo assessment and ex vivo comparison.

BACKGROUND: The brainstem contains grey matter nuclei and white matter tracts to be identified in clinical practice. The small size and the low contrast among them make their in vivo visualisation challenging using conventional magnetic resonance imaging (MRI) sequences at high magnetic field strengths. Combining higher spatial resolution, signal- and contrast-to-noise ratio and sensitivity to magnetic susceptibility (χ), susceptibility-weighted 7-T imaging could improve the assessment of brainstem anatomy. METHODS: We acquired high-resolution 7-T MRI of the brainstem in a 46-year-old female healthy volunteer (using a three-dimensional multi-echo gradient-recalled-echo sequence; spatial resolution 0.3 × 0.3 × 1.2 mm3) and in a brainstem sample from a 48-year-old female body donor that was sectioned and stained. Images were visually assessed; nuclei and tracts were labelled and named according to the official nomenclature. RESULTS: This in vivo imaging revealed structures usually evaluated through light microscopy, such as the accessory olivary nuclei, oculomotor nucleus and the medial longitudinal fasciculus. Some fibre tracts, such as the medial lemniscus, were visible for most of their course. Overall, in in vivo acquisitions, χ and frequency maps performed better than T2*-weighted imaging and allowed for the evaluation of a greater number of anatomical structures. All the structures identified in vivo were confirmed by the ex vivo imaging and histology. CONCLUSIONS: The use of multi-echo GRE sequences at 7 T allowed the visualisation of brainstem structures that are not visible in detail at conventional magnetic field and opens new perspectives in the diagnostic and therapeutical approach to brain disorders. RELEVANCE STATEMENT: In vivo MR imaging at UHF provides detailed anatomy of CNS substructures comparable to that obtained with histology. Anatomical details are fundamentals for diagnostic purposes but also to plan a direct targeting for a minimally invasive brain stimulation or ablation. KEY POINTS: • The in vivo brainstem anatomy was explored with ultrahigh field MRI (7 T). • In vivo T2*-weighted magnitude, χ, and frequency images revealed many brainstem structures. • Ex vivo imaging and histology confirmed all the structures identified in vivo. • χ and frequency imaging revealed more brainstem structures than magnitude imaging.

Mutable Collagenous Tissue Isolated from Echinoderms Leads to the Production of a Dermal Template That Is Biocompatible and Effective for Wound Healing in Rats.

The mutable collagenous tissue (MCT) of echinoderms possesses biological peculiarities that facilitate native collagen extraction and employment for biomedical applications such as regenerative purposes for the treatment of skin wounds. Strategies for skin regeneration have been developed and dermal substitutes have been used to cover the lesion to facilitate cell proliferation, although very little is known about the application of novel matrix obtained from marine collagen. From food waste we isolated eco-friendly collagen, naturally enriched with glycosaminoglycans, to produce an innovative marine-derived biomaterial assembled as a novel bi-layered skin substitute (Marine Collagen Dermal Template or MCDT). The present work carried out a preliminary experimental in vivo comparative analysis between the MCDT and Integra, one of the most widely used dermal templates for wound management, in a rat model of full-thickness skin wounds. Clinical, histological, and molecular evaluations showed that the MCDT might be a valuable tool in promoting and supporting skin wound healing: it is biocompatible, as no adverse reactions were observed, along with stimulating angiogenesis and the deposition of mature collagen. Therefore, the two dermal templates used in this study displayed similar biocompatibility and outcome with focus on full-thickness skin wounds, although a peculiar cellular behavior involving the angiogenesis process was observed for the MCDT.

Development and preclinical evaluation of bioactive nerve conduits for peripheral nerve regeneration: A comparative study.

In severe peripheral nerve injuries, nerve conduits (NCs) are good alternatives to autografts/allografts; however, the results the available devices guarantee for are still not fully satisfactory. Herein, differently bioactivated NCs based on the new polymer oxidized polyvinyl alcohol (OxPVA) are compared in a rat model of sciatic nerve neurotmesis (gap: 5 mm; end point: 6 weeks). Thirty Sprague Dawley rats are randomized to 6 groups: Reverse Autograft (RA); Reaxon®; OxPVA; OxPVA + EAK (self-assembling peptide, mechanical incorporation); OxPVA + EAK-YIGSR (mechanical incorporation); OxPVA + Nerve Growth Factor (NGF) (adsorption). Preliminarily, all OxPVA-based devices are comparable with Reaxon® in Sciatic Functional Index score and gait analysis; moreover, all conduits sustain nerve regeneration (S100, ß-tubulin) without showing substantial inflammation (CD3, F4/80) evidences. Following morphometric analyses, OxPVA confirms its potential in PNI repair (comparable with Reaxon®) whereas OxPVA + EAK-YIGSR stands out for its myelinated axons total number and density, revealing promising in injury recovery and for future application in clinical practice.

Hearing and Seeing Nerve/Tendon Snapping: A Systematic Review on Dynamic Ultrasound Examination.

Nerve/tendon snapping can occur due to their sudden displacement during the movement of an adjacent joint, and the clinical condition can really be painful. It can actually be challenging to determine the specific anatomic structure causing the snapping in various body regions. In this sense, ultrasound examination, with all its advantages (especially providing dynamic imaging), appears to be quite promising. To date, there are no comprehensive reviews reporting on the use of dynamic ultrasound examination in the diagnosis of nerve/tendon snapping. Accordingly, this article aims to provide a substantial discussion as to how US examination would contribute to 'seeing' and 'hearing' these pathologies' different maneuvers/movements.

Crural and Plantar Fasciae Changes in Chronic Charcot Diabetic Foot: A Cross-Sectional Ultrasound Imaging Study-An Evidence of Fascial Continuity.

Crural fascia (CF) and plantar fascia (PF) are biomechanically crucial in the gait and in the proprioception, particularly in the propulsion phase of the foot during the gait cycle and in the dissipation of forces during weight-bearing activities. Recent studies have revealed an association between increases in PF thickness and diabetes. The purpose of this study was to measure and compare by ultrasound (US) imaging the thickness of the CF and PF at different regions/levels in chronic Charcot diabetic foot patients (group 1) and in healthy volunteers (group 2). A cross-sectional study was performed using US imaging to measure the CF with Pirri et al.'s protocol and PF with a new protocol in a sample of 31 subjects (15 patients and 16 healthy participants). The findings for CF and PF revealed statistically significant differences in the poster region of CF (Post 1: group 1 vs. group 2: p = 0.03; Post 2: group 1 vs. group 2: p = 0.03) and in PF at two different levels (PF level 1: group 1 vs. group 2: p < 0.0001; PF level 2: group 1 vs. group 2: p < 0.0001). These findings suggest that chronic Charcot diabetic foot patients have CF and PF thicker compared to healthy volunteers. The US examination suggests that fascial thicknesses behavior in these patients points out altered fascial remodeling due to diabetes pathology and biomechanical changes.

Neurotransmitter and receptor systems in the subthalamic nucleus.

The Subthalamic Nucleus (STh) is a lens-shaped subcortical structure located ventrally to the thalamus, that despite being embryologically derived from the diencephalon, is functionally implicated in the basal ganglia circuits. Because of this strict structural and functional relationship with the circuits of the basal ganglia, the STh is a current target for deep brain stimulation, a neurosurgical procedure employed to alleviate symptoms in movement disorders, such as Parkinson's disease and dystonia. However, despite the great relevance of this structure for both basal ganglia physiology and pathology, the neurochemical and molecular anatomy of the STh remains largely unknown. Few studies have specifically addressed the detection of neurotransmitter systems and their receptors within the structure, and even fewer have investigated their topographical distribution. Here, we have reviewed the scientific literature on neurotransmitters relevant in the STh function of rodents, non-human primates and humans including glutamate, GABA, dopamine, serotonin, noradrenaline with particular focus on their subcellular, cellular and topographical distribution. Inter-species differences were highlighted to provide a framework for further research priorities, particularly in humans.

Bridging Gaps in Peripheral Nerves: From Current Strategies to Future Perspectives in Conduit Design.

In peripheral nerve injuries (PNI) with substance loss, where tensionless end-to-end suture is not achievable, the positioning of a graft is required. Available options include autografts (e.g., sural nerve, medial and lateral antebrachial cutaneous nerves, superficial branch of the radial nerve), allografts (Avance®; human origin), and hollow nerve conduits. There are eleven commercial hollow conduits approved for clinical, and they consist of devices made of a non-biodegradable synthetic polymer (polyvinyl alcohol), biodegradable synthetic polymers (poly(DL-lactide-ε-caprolactone); polyglycolic acid), and biodegradable natural polymers (collagen type I with/without glycosaminoglycan; chitosan; porcine small intestinal submucosa); different resorption times are available for resorbable guides, ranging from three months to four years. Unfortunately, anatomical/functional nerve regeneration requirements are not satisfied by any of the possible alternatives; to date, focusing on wall and/or inner lumen organization/functionalization seems to be the most promising strategy for next-generation device fabrication. Porous or grooved walls as well as multichannel lumens and luminal fillers are the most intriguing options, eventually also including the addition of cells (Schwann cells, bone marrow-derived, and adipose tissue derived stem cells) to support nerve regeneration. This review aims to describe common alternatives for severe PNI recovery with a highlight of future conduits.

Antibiotic Treatment Induces Long-Lasting Effects on Gut Microbiota and the Enteric Nervous System in Mice.

The side effects of antibiotic treatment directly correlate with intestinal dysbiosis. However, a balanced gut microbiota supports the integrity of the enteric nervous system (ENS), which controls gastrointestinal neuromuscular functions. In this study, we investigated the long-term effects of antibiotic-induced microbial dysbiosis on the ENS and the impact of the spontaneous re-establishment of the gut microbiota on gastrointestinal functions. C57BL/6J mice were treated daily for two weeks with antibiotics. After 0-6 weeks of antibiotics wash-out, we determined (a) gut microbiota composition, (b) gastrointestinal motility, (c) integrity of the ENS, (d) neurochemical code, and (e) inflammation. Two weeks of antibiotic treatment significantly altered gut microbial composition; the genera Clostridium, Lachnoclostridium, and Akkermansia did not regain their relative abundance following six weeks of antibiotic discontinuation. Mice treated with antibiotics experienced delayed gastrointestinal transit and altered expression of neuronal markers. The anomalies of the ENS persisted for up to 4 weeks after the antibiotic interruption; the expression of neuronal HuC/D, glial-derived neurotrophic factor (Gdnf), and nerve growth factor (Ngf) mRNA transcripts did not recover. In this study, we strengthened the idea that antibiotic-induced gastrointestinal dysmotility directly correlates with gut dysbiosis as well as structural and functional damage to the ENS.

Sono-palpation and sono-Tinel in musculoskeletal ultrasound examination: use all "sono-senses". A systematic review.

Flexibility and dynamic perspective of ultrasound imaging allow for a targeted/focused examination, yielding extra find-ings. Sonopalpation - also referred as sono-Tinel for nerves - is one of those particular features of ultrasound examination whereby the ultrasound probe is actively 'manipulated'. It is paramount to ascertain the painful structure/pathology during the evaluation of a patient and it is not possible with other imaging techniques other than ultrasonography. In this aspect, the cur-rent review aims to provide an analysis of the literature regarding the use of sonopalpation for clinical and research purposes respectively.

The transversoclasiotome: a novel instrument for examining the vertebral artery.

Opening the foramen transversarium of the cervical vertebrae is necessary for accessing the vertebral vessels. There are no specialist tools for cutting the anterior lamina of the transverse processes, and alternatives lead to questionable results. A novel tool, the transversoclasiotome, is described and tested. The literature and patent databases were systematically reviewed. A blueprint of the transversoclasiotome was created, and the prototype was tested through autopsy on ten fresh-frozen cadavers within our Body Donation Program. The transversoclasiotome consists of two delicate branches mounted as a scissor, one a cutting jaw and the other a knocker with a rounded tip, both angled 30° to the principal axis. The jaws shut, facing each other in parallel. The cutting jaw corresponds to a slit on the knocker profile without protruding beyond it even when entirely closed. It acts by cutting and wedging. The testing autopsies demonstrated its suitability for its purpose, with an adequate response to the pressure exerted on the bone lamina. The section cut cleanly, without sliding off while closing on the bone. The vertebral vessels were not injured either during instrument insertion or cutting. Their morphological features are described. The transversoclasiotome has been proven appropriate for sectioning the anterior lamina of transverse processes of the cervical vertebrae. It meets the needs of clinical anatomy in teaching and training clinicians or surgeons, forensic clinical anatomy during medico-legal investigation, and research.

Ultrasound Imaging of Thoracolumbar Fascia Thickness: Chronic Non-Specific Lower Back Pain versus Healthy Subjects; A Sign of a "Frozen Back"?

The thoracolumbar fascia (TLF) plays an important role in lower back pain (LBP). Recent studies have revealed an association between increases in TLF thickness and reduced TLF gliding in patients with LBP. The purpose of this study was to measure and compare by ultrasound (US) imaging the thickness of the TLF at the bilateral L3 level of the lumbar spine in the longitudinal and transverse axes in chronic non-specific LBP and in healthy subjects. A cross-sectional study was performed using US imaging to measure the longitudinal and transverse axes with a new protocol in a sample of 92 subjects: 46 chronic non-specific LBP patients and 46 healthy participants. The findings for TLF thickness revealed statistically significant differences (p < 0.05) in the longitudinal and transverse axes between the two groups. Moreover, in the healthy group, a statistically significant difference was found between the longitudinal and transverse axes (p = 0.001 for left and p = 0.02 for right), which was not evident in the LBP patients. These findings suggest that the LBP patients lost anisotropy of the TLF, with it becoming homogeneously thicker and losing adaptability in the transversal direction. The US imaging evaluation suggests that TLF thickness behavior points out altered fascial remodelling compared to healthy subjects, a sort of "frozen back".