Sports-related concussions may cause white matter injuries and persistent post-concussive symptoms (PPCS). We hypothesized that athletes with PPCS would have neurocognitive impairments and white matter abnormalities that could be revealed by advanced neuroimaging using ultra-high field strength diffusion tensor (DTI) and diffusion kurtosis (DKI) imaging metrics and cerebrospinal fluid (CSF) biomarkers. A cohort of athletes with PPCS severity limiting the ability to work/study and participate in sport school and/or social activities for ≥6 months completed 7T magnetic resonance imaging (MRI) (morphological T1-weighed volumetry, DTI and DKI), extensive neuropsychological testing, symptom rating, and CSF biomarker sampling.
View Article and Find Full Text PDFForensic Sci Med Pathol
September 2024
The appearance of a gunshot wound (GSW) is greatly influenced by the velocity of the projectile, where high-velocity projectiles (HVPs) are defined as ballistic agents reaching a muzzle velocity of > 600 m/s fired from assault rifles. The aim of the study is to present and explain the differences in the dimensions of entrance and exit wounds between the most used handguns and assault rifles and to propose a predictor of HVP, i.e.
View Article and Find Full Text PDFThe management of cancer with alternative approaches is a matter of clinical interest worldwide. High-intensity focused ultrasound (HIFU) surgery is a noninvasive technique performed under US or MRI guidance. The most studied therapeutic uses of HIFU involve thermal tissue ablation, demonstrating both palliative and curative potential.
View Article and Find Full Text PDFIntroduction: Recent advances in human cardiac 3D approaches have yielded progressively more complex and physiologically relevant culture systems. However, their application in the study of complex pathological processes, such as inflammation and fibrosis, and their utility as models for drug development have been thus far limited.
Methods: In this work, we report the development of chamber-specific, vascularised human induced pluripotent stem cell-derived cardiac microtissues, which allow for the multi-parametric assessment of cardiac fibrosis.
A history of infection has been linked with increased risk of acute myeloid leukaemia (AML) and related myelodysplastic syndromes (MDS). Furthermore, AML and MDS patients suffer frequent infections because of disease-related impaired immunity. However, the role of infections in the development and progression of AML and MDS remains poorly understood.
View Article and Find Full Text PDFMitochondrial dysfunction involving mitochondria-associated ER membrane (MAM) dysregulation is implicated in the pathogenesis of late-onset neurodegenerative diseases, but understanding is limited for rare early-onset conditions. Loss of the MAM-resident protein WFS1 causes Wolfram syndrome (WS), a rare early-onset neurodegenerative disease that has been linked to mitochondrial abnormalities. Here we demonstrate mitochondrial dysfunction in human induced pluripotent stem cell-derived neuronal cells of WS patients.
View Article and Find Full Text PDFPurpose: To assess the diagnostic performance of Whole Body (WB)-MRI in comparison with 18F-Fluorodeoxyglucose-PET/CT (18F-FDG-PET/CT) in lymphoma staging and to assess whether quantitative metabolic parameters from 18F-FDG-PET/CT and Apparent Diffusion Coefficient (ADC) values are related.
Materials And Methods: We prospectively enrolled patients with a histologically proven primary nodal lymphoma to undergo 18F-FDG-PET/CT and WB-MRI, both performed within 15 days one from the other, either before starting treatment (baseline) or during treatment (interim). Positive and negative predictive values of WB-MRI for the identification of nodal and extra-nodal disease were measured.
The inefficacy of antibiotics against Gram-negative bacteria is a major challenge for treatment of many clinically important bacterial infections. The complex structure of the double cell membrane of Gram-negative bacteria makes it inaccessible to many key antibiotics such as vancomycin and also presents a major challenge for drug development. In this study we design of a novel hybrid silica nanoparticle system bearing membrane targeting groups with the antibiotic encapsulated together with a ruthenium luminescent tracking agent, for optical detection of the nanoparticle delivery in the bacterial cell.
View Article and Find Full Text PDFBackground Evidence regarding effective nonsurgical management of sciatica remains limited. Purpose To determine a difference in effectiveness between combined pulsed radiofrequency (PRF) and transforaminal epidural steroid injection (TFESI) treatment versus TFESI alone for sciatic pain due to lumbar disk herniation. Materials and Methods This prospective multicenter double-blind randomized clinical trial was conducted between February 2017 and September 2019 in participants with sciatica due to lumbar disk herniation lasting 12 weeks or longer that was not responsive to conservative treatment.
View Article and Find Full Text PDFBackground Recent consensus statements and clinical trials have assessed the value of MRI-guided focused ultrasound surgery for pain palliation of bone metastases; however, a comparison with external beam radiation therapy (EBRT) has not been performed. Purpose To compare safety and effectiveness data of MRI-guided focused ultrasound and EBRT in the treatment of bone metastases. Materials and Methods Participants with painful bone metastases, excluding skull and vertebral bodies, were enrolled in a prospective open-label nonrandomized phase II study between January 2017 and May 2019 and underwent either MRI-guided focused ultrasound or EBRT.
View Article and Find Full Text PDFSymptoms of vestibular dysfunction such as dizziness and vertigo are common after sports-related concussions (SRC) and associated with a worse outcome and a prolonged recovery. Vestibular dysfunction after SRC can be because of an impairment of the peripheral or central neural parts of the vestibular system. The aim of the present study was to establish the cause of vestibular impairment in athletes with SRC who have persisting post-concussive symptoms (PPCS).
View Article and Find Full Text PDFBackground: We previously demonstrated the in vitro killing of AML cells by the combination of the lipid-lowering agent bezafibrate (BEZ) and the contraceptive hormone medroxyprogesterone acetate (MPA). A phase II trial demonstrated in vivo safety and efficacy of BEZ and MPA (BaP) in elderly, relapsed/refractory AML and high-risk myelodysplastic syndrome (MDS) patients. However, we observed dose-limiting toxicities in a second trial that attempted to improve outcomes via escalation of BaP doses.
View Article and Find Full Text PDFA non-tuberculous mycobacterium, is an emerging opportunistic pathogen associated with difficult to treat pulmonary infections, particularly in patients suffering from cystic fibrosis. It is capable of forming biofilms that result in an increase of already high levels of antibiotic resistance in this bacterium. Evidence that forms biofilm-like microcolonies in patient lungs and on medical devices further implicated the need to investigate this biofilm in detail.
View Article and Find Full Text PDFIn root canal therapy, irrigating solutions are employed to eliminate the bacterial load and also prepare dentin for sealer interaction. The aim of this research was to assess how irrigating solutions employed on their own or in sequence affected the tooth structure. The best way to prepare the tooth for obturation using hydraulic calcium silicate cement (HCSC) sealers and gutta-percha, thus guiding clinicians on a matched irrigation-obturation strategy for optimized root canal treatment was investigated.
View Article and Find Full Text PDFLumbosacral disc herniation (LDH) represents the most common cause of sciatica. Currently, there is limited evidence about minimally invasive interventional therapies for the treatment of this condition. This paper presents the protocol for a multicenter, prospective, randomized, controlled, phase III trial evaluating if PRF in addition to TFESI leads to better outcomes in patients with sciatica due to LDH, compared to TFESI alone, during the first year after treatment (Pulsed Radiofrequency in Addition to TFESI for Sciatica [PRATS]).
View Article and Find Full Text PDFis an environmental, non-tuberculous mycobacterial species, capable of causing infections in humans. Biofilm formation is a key strategy used by in colonising niches in the environment and in the host. We studied a water-air interface (pellicle) biofilm of using a wide array of approaches to outline the molecular structure and composition of the biofilm.
View Article and Find Full Text PDFA disintegrin and metalloprotease 10 (ADAM10) is a transmembrane protein essential for embryonic development, and its dysregulation underlies disorders such as cancer, Alzheimer's disease, and inflammation. ADAM10 is a "molecular scissor" that proteolytically cleaves the extracellular region from >100 substrates, including Notch, amyloid precursor protein, cadherins, growth factors, and chemokines. ADAM10 has been recently proposed to function as six distinct scissors with different substrates, depending on its association with one of six regulatory tetraspanins, termed TspanC8s.
View Article and Find Full Text PDFNanomaterial (NM) surface chemistry has an established and significant effect on interactions at the nano-bio interface, with important toxicological consequences for manufactured NMs, as well as potent effects on the pharmacokinetics and efficacy of nano-therapies. In this work, the effects of different surface modifications (PVP, Dispex AA4040, and Pluronic F127) on the uptake, cellular distribution, and degradation of titanium dioxide NMs (TiO NMs, ~10 nm core size) are assessed and correlated with the localization of fluorescently-labeled serum proteins forming their coronas. Imaging approaches with an increasing spatial resolution, including automated high throughput live cell imaging, correlative confocal fluorescence and reflectance microscopy, and dSTORM super-resolution microscopy, are used to explore the cellular fate of these NMs and their associated serum proteins.
View Article and Find Full Text PDFAntimicrobial-resistant (AMR) infections pose a serious risk to human and animal health. A major factor contributing to this global crisis is the sharing of resistance genes between different bacteria via plasmids. The WHO lists , such as and , producing extended-spectrum β-lactamases (ESBL) and carbapenemases as "critical" priorities for new drug development.
View Article and Find Full Text PDFBackground: Pseudomonas aeruginosa is an opportunistic bacterium that infects the airways of cystic fibrosis patients, surfaces of surgical and burn wounds, and indwelling medical devices. Patients are prone to secondary fungal infections, with Candida albicans being commonly co-isolated with P. aeruginosa.
View Article and Find Full Text PDFCa entry Orai1 store-operated Ca channels in the plasma membrane is critical to cell function, and Orai1 loss causes severe immunodeficiency and developmental defects. The tetraspanins are a superfamily of transmembrane proteins that interact with specific 'partner proteins' and regulate their trafficking and clustering. The aim of this study was to functionally characterize tetraspanin Tspan18.
View Article and Find Full Text PDFWe investigated the physical role of the extracellular matrix (ECM) in vascular homeostasis in the basal chordate , which has a large, transparent, extracorporeal vascular network encompassing an area >100 cm We found that the collagen cross-linking enzyme lysyl oxidase is expressed in all vascular cells and that in vivo inhibition using β-aminopropionitrile (BAPN) caused a rapid, global regression of the entire network, with some vessels regressing >10 mm within 16 h. BAPN treatment changed the ultrastructure of collagen fibers in the vessel basement membrane, and the kinetics of regression were dose dependent. Pharmacological inhibition of both focal adhesion kinase (FAK) and Raf also induced regression, and levels of phosphorylated FAK in vascular cells decreased during BAPN treatment and FAK inhibition but not Raf inhibition, suggesting that physical changes in the vessel ECM are detected via canonical integrin signaling pathways.
View Article and Find Full Text PDFGE81112 is a tetrapeptide antibiotic that binds to the 30S ribosomal subunit and specifically inhibits P-site decoding of the mRNA initiation codon by the fMet-tRNA anticodon. GE81112 displays excellent microbiological activity against some Gram-positive and Gram-negative bacteria in both minimal and complete, chemically defined, broth, but is essentially inactive in complete complex media. This is due to the presence of peptides that compete with the antibiotic for the oligopeptide permease system (Opp) responsible for its illicit transport into the bacterial cells as demonstrated in the cases of Escherichia coli and Bacillus subtilis.
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