Search Results (8)

Background: This study aims to investigate the biomechanical characteristics of orthodontic miniscrews manufactured for use in infrazygomatic crests. Methods: This study analyzed the Zygomatic Spider Screw (HDC, Thiene, Italy), considering four variables: length, insertion angle, insertion depth, support thickness. Twenty-two configurations were tested on 66 miniscrews, all with a diameter of 2 mm, and were inserted into D1 bone-like supports. After compression tests, the deformation angles and linear distances between the tips of the miniscrews were measured. Results: Power analysis showed 99% power for the deformation angles and linear distance. The ICC indicated the good repeatability of the results, with values above 0.70. The mean maximum load values ranged from 21.5 N to 228.8 N, while the mean deformations ranged from 0.45 mm to 2.26 mm. Miniscrews with greater insertion depths (6 and 8 mm) exhibited approximately twice the average deformation (1.5 mm) compared to those inserted at 2 and 4 mm (0.71 mm). It was noted that miniscrews with higher deformation and a lower applied load were those with a working part length of 10 mm and an insertion depth of 2 mm, while those with lower deformation and a better load-bearing capacity were those with a working part length of 6 mm that were fully inserted into the bone support. Conclusions: The miniscrew design and insertion depth significantly affect biomechanical properties. It is advisable to maximize the insertion depth and minimize the distance between the support and the point of force application. The insertion angle did not prove to be a determining factor in the load. Full article

Desert strains of the genus Chroococcidiopsis are among the most desiccation-resistant cyanobacteria capable of anhydrobiosis. The accumulation of two sugars, sucrose and trehalose, facilitates the entrance of anhydrobiotes into a reversible state of dormancy by stabilizing cellular components upon water removal. This study aimed to evaluate, at the atomistic level, the role of trehalose in desiccation resistance by using as a model system the 30S ribosomal subunit of the desert cyanobacterium Chroococcidiopsis sp. 029. Molecular dynamic simulations provided atomistic evidence regarding its protective role on the 30S molecular structure. Trehalose forms an enveloping shell around the ribosomal subunit and stabilizes the structures through a network of direct interactions. The simulation confirmed that trehalose actively interacts with the 30S ribosomal subunit and that, by replacing water molecules, it ensures ribosomal structural integrity during desiccation, thus enabling protein synthesis to be carried out upon rehydration. Full article

The ocular surface is a complex structure that includes cornea, conjunctiva, limbus, and tear film, and is critical for maintaining visual function. When the ocular-surface integrity is altered by a disease, conventional therapies usually rely on topical drops or tissue replacement with more invasive procedures, such as corneal transplants. However, in the last years, regeneration therapies have emerged as a promising approach to repair the damaged ocular surface by stimulating cell proliferation and restoring the eye homeostasis and function. This article reviews the different strategies employed in ocular-surface regeneration, including cell-based therapies, growth-factor-based therapies, and tissue-engineering approaches. Dry eye and neurotrophic keratopathy diseases can be treated with nerve-growth factors to stimulate the limbal stem-cell proliferation and the corneal nerve regeneration, whereas conjunctival autograft or amniotic membrane are used in subjects with corneal limbus dysfunction, such as limbal stem-cell deficiency or pterygium. Further, new therapies are available for patients with corneal endothelium diseases to promote the expansion and migration of cells without the need of corneal keratoplasty. Finally, gene therapy is a promising new frontier of regeneration medicine that can modify the gene expression and, potentially, restore the corneal transparency by reducing fibrosis and neovascularization, as well as by stimulating stem-cell proliferation and tissue regeneration. Full article

The aim of this retrospective study was to investigate the longitudinal body changes in terms of muscle and adipose areas and their prognostic role in elderly (>65 years) patients affected by Hodgkin lymphoma (HL). Skeletal muscle area (SMA), skeletal muscle index (SMI), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intramuscular adipose tissue (IMAT), and total dispose tissue (TAT) were measured using the computed tomography (CT) of fluorine-18-fluorodeoxyglucose positron emission tomography/CT ([18F]FDG PET/CT) in 88 patients who undertook baseline, interim (after two cycles of chemotherapy), and end-of-treatment (after 6 cycles of chemotherapy) PET/CT scans. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured at pre-treatment PET/CT. Metabolic response applying Deauville score was evaluated at interim and end-of-treatment PET/CT. Survival curves, such as progression free survival (PFS) and overall survival (OS), were calculated for the whole population. Fifty-eight (66%) patients had sarcopenia at baseline and sarcopenia rate increased at interim scan with 68 (77%) cases and at end-of-treatment scan with 73 (83%) cases. Muscular areas (SMA and SMI) declined significantly during the treatment (p < 0.001), decreasing from baseline by 5% and 7% at interim and end-of-treatment evaluation, respectively. Instead, VAT, SAT, IMAT, and TAT increased significantly over this time (p < 0.001). Sarcopenia was significantly related with comprehensive geriatric assessment. PET/CT response at interim and end-of-treatment, MTV, TLG, and baseline sarcopenia were independent prognostic factors for PFS. Instead, metabolic response at interim and end-of-treatment PET, baseline sarcopenia, ΔSMI at interim, and ΔSMI at end-of-treatment for OS were independent prognostic factors. Full article

Background and purpose: Although chemotherapy, biological agents, and radiotherapy (RT) are cornerstones of the treatment of multiple myeloma (MM), the literature regarding the possible interactions of concurrent systemic treatment (CST) and RT is limited, and the optimal RT dose is still unclear. Materials and methods: We retrospectively analyzed the records of patients who underwent RT for MM at our institution from 1 January 2005 to 30 June 2020. The data of 312 patients and 577 lesions (treated in 411 accesses) were retrieved. Results: Most of the treated lesions involved the vertebrae (60%) or extremities (18.9%). Radiotherapy was completed in 96.6% of the accesses and, although biologically effective doses assuming an α/β ratio of 10 (BED 10) > 38 Gy and CST were significantly associated with higher rates of toxicity, the safety profile was excellent, with side effects grade ≥2 reported only for 4.1% of the accesses; CST and BED 10 had no impact on the toxicity at one and three months. Radiotherapy resulted in significant improvements in performance status and in a pain control rate of 87.4% at the end of treatment, which further increased to 96.9% at three months and remained at 94% at six months. The radiological response rate at six months (data available for 181 lesions) was 79%, with only 4.4% of lesions in progression. Progression was significantly more frequent in the lesions treated without CST or BED 10 < 15 Gy, while concurrent biological therapy resulted in significantly lower rates of progression. Conclusion: Radiotherapy resulted in optimal pain control rates and fair toxicity, regardless of BED 10 and CST; the treatments with higher BED 10 and CST (remarkably biological agents) improved the already excellent radiological disease control. Full article

Galectin-3 is a carbohydrate-binding protein and the most studied member of the galectin family. It regulates several functions throughout the body, among which are inflammation and post-injury remodelling. Recent studies have highlighted the similarity between Galectin-3′s carbohydrate recognition domain and the so-called “galectin fold” present on the N-terminal domain of the S1 sub-unit of the SARS-CoV-2 spike protein. Sialic acids binding to the N-terminal domain of the Spike protein are known to be crucial for viral entry into humans, and the role of Galectin-3 as a mediator of lung fibrosis has long been the object of study since its levels have been found to be abnormally high in alveolar macrophages following lung injury. In this context, the discovery of a double inhibitor may both prevent viral entry and reduce post-infection pulmonary fibrosis. In this study, we use a database of 56 compounds, among which 37 have known experimental affinity with Galectin-3. We carry out virtual screening of this database with respect to Galectin-3 and Spike protein. Several ligands are found to exhibit promising binding affinity and interaction with the Spike protein’s N-terminal domain as well as with Galectin-3. This finding strongly suggests that existing Galectin-3 inhibitors possess dual-binding capabilities to disrupt Spike–ACE2 interactions. Herein we identify the most promising inhibitors of Galectin-3 and Spike proteins, of which five emerge as potential dual effective inhibitors. Our preliminary results warrant further in vitro and in vivo testing of these putative inhibitors against SARS-CoV-2 with the hope of being able to halt the spread of the virus in the future. Full article

Aims: It is debated whether the NRAS-mutant melanoma is more aggressive than NRAS wildtype. It is equally controversial whether NRAS-mutant metastatic melanoma (MM) is more responsive to checkpoint inhibitor immunotherapy (CII). 331 patients treated with CII as first-line were retrospectively recruited: 162 NRAS-mutant/BRAF wild-type (mut/wt) and 169 wt/wt. We compared the two cohorts regarding the characteristics of primary and metastatic disease, disease-free interval (DFI) and outcome to CII. No substantial differences were observed between the two groups at melanoma onset, except for a more frequent ulceration in the wt/wt group (p = 0.03). Also, the DFI was very similar in the two cohorts. In advanced disease, we only found lung and brain progression more frequent in the wt/wt group. Regarding the outcomes to CII, no significant differences were reported in overall response rate (ORR), disease control rate (DCR), progression free survival (PFS) or overall survival (OS) (42% versus 37%, 60% versus 59%, 12 (95% CI, 7–18) versus 9 months (95% CI, 6–16) and 32 (95% CI, 23–49) versus 27 months (95% CI, 16–35), respectively). Irrespectively of mutational status, a longer OS was significantly associated with normal LDH, <3 metastatic sites, lower white blood cell and platelet count, lower neutrophil-to-lymphocyte (N/L) ratio. Our data do not show increased aggressiveness and higher responsiveness to CII in NRAS-mutant MM. Full article

Bifidobacterium longum (B. longum) ES1 is a probiotic strain capable of modulating microbiome composition, anti-inflammatory activity and intestinal barrier function. We investigated the use of B. Longum ES1 in the treatment of patients with diarrhoea-predominant irritable bowel syndrome (IBS-D). Sixteen patients were treated for 8 or 12 weeks with B. Longum ES1 (1 × 10⁹ CFU/day). Serum zonulin and cytokines were measured at baseline (T0) and at the end of therapy (T1). Clinical response to therapy was assessed by IBS Severity Scoring System. Interleukin (IL)-6, IL-8, IL-12p70 and tumor necrosis factor (TNF) α levels decreased from T0 to T1, irrespective of treatment duration (p < 0.05), while zonulin levels diminished only in patients treated for 12 weeks (p = 0.036). Clinical response was observed in 5/16 patients (31%): 4/8 (50%) treated for 12 weeks and 1/8 (13%) treated for 8 weeks. Abdominal pain improved only in patients treated for 12 weeks (5/8 vs. 0/8, p = 0.025), while stool consistency improved regardless of therapy duration (p < 0.001). In conclusion, the results of this pilot study showed, in IBS-D patients treated for 12 weeks with B. longum ES1, a reduction in the levels of pro-inflammatory cytokines, and intestinal permeability as well as an improvement in gastrointestinal symptoms, but further studies including a placebo-control group are necessary to prove a causal link. Full article