The Role of Tropomyosin and Cardiac Myosin Binding Protein-C in Modulating Thin Filament Activity

Muscle contraction is a finely tuned mechanism involving cyclical interactions between actin and myosin, regulated by calcium through troponin and tropomyosin and modulated by myosin binding protein-C. Genetic mutations of the proteins involved in such complex mechanism can thus lead to potential life threatening diseases, such as Hypertrophic Cardiomyopathy (HCM). Although being mostly asymptomatic, HCM affects 1 in 500 people, ultimately leading to poor prognosis and sudden death, thought to occur through the impairment of relaxation during diastole. In this thesis I present the experiments conducted to improve our current understanding of the molecular mechanism behind HCM, specifically on the role of tropomyosin and myosin binding protein-C in modulating thin filament activation and relaxation. Using a single molecule approach, we first visualised fluorescent myosin binding to reconstituted thin filaments and examined their dynamics in the presence of the tropomyosin HCM causing E180G mutation, demonstrating a shift of the thin filament activation state towards the closed state, facilitating myosin binding at low calcium, and a reduction of the thin filament regulatory unit. We then looked at the dynamics of very highly concentrated clusters of myosin, showing how the sudden collapse of these active regions cannot be explained by normal relaxation mechanisms, thus suggesting an alternative mechanistic role for tropomyosin and how its mutations could lead to impaired relaxation in HCM. Finally, we turned our focus on N-terminal fragments of cardiac myosin binding protein-C (cMyBP-C) and study their role in thin filament activation, by looking at how they affect acto-myosin interactions. We found that only the presence of the whole cMyBP-C N-terminus was able to promote acto-myosin interactions at low Ca2+ or repressing them at high Ca2+. Moreover, by looking at the dynamics of the fragments, we were able to determine that cMyBP-C possesses a two steps binding mechanism to actin, leading us to define its mechanism by which it activates the thin filament

Advances in Preventive and Therapeutic Approaches for Dental Erosion: A Systematic Review

This review discusses both preventive measures and clinically implemented therapy procedures that have been developed recently for the prevention and treatment of tooth erosion. Methods: The databases PubMed, Scopus, and Web of Science were used for a thorough search. Studies on the prevention and treatment of dental erosion that were conducted in English and used in vitro were among the inclusion criteria. Results: The search turned up 391 papers in total, with 34 of those publications matching the requirements for inclusion. Varnishes, toothpastes, and solutions containing fluoride and other substances were used as preventive measures. Conclusions: Dental erosion is a significant issue, and taking preventative steps is crucial to lessening the disease’s spread and its effects. Interventions based on fluoride seem to be successful at halting erosion and encouraging remineralization. To effectively address severe tooth erosion, therapeutic methods, including composite restorations, prosthetic crowns, and veneers, are available. Dental erosion causes aesthetic and functional issues that are best addressed with less invasive treatments like direct composite restorations. To improve and broaden the range of available treatments for this common dental issue, additional research and development are required

Artificial Intelligence and Its Clinical Applications in Orthodontics: A Systematic Review

This review aims to analyze different strategies that make use of artificial intelligence to enhance diagnosis, treatment planning, and monitoring in orthodontics. Orthodontics has seen significant technological advancements with the introduction of digital equipment, including cone beam computed tomography, intraoral scanners, and software coupled to these devices. The use of deep learning in software has sped up image processing processes. Deep learning is an artificial intelligence technology that trains computers to analyze data like the human brain does. Deep learning models are capable of recognizing complex patterns in photos, text, audio, and other data to generate accurate information and predictions. Materials and Methods: Pubmed, Scopus, and Web of Science were used to discover publications from 1 January 2013 to 18 October 2023 that matched our topic. A comparison of various artificial intelligence applications in orthodontics was generated. Results: A final number of 33 studies were included in the review for qualitative analysis. Conclusions: These studies demonstrate the effectiveness of AI in enhancing orthodontic diagnosis, treatment planning, and assessment. A lot of articles emphasize the integration of artificial intelligence into orthodontics and its potential to revolutionize treatment monitoring, evaluation, and patient outcomes

Predictability of Dental Distalization with Clear Aligners: A Systematic Review

The current review aims to evaluate the scientific evidence relating to the effectiveness of treatment with clear aligners (CAs) in controlling distalization orthodontic tooth movement. “Orthodontics, aligners” and “distalization” were the search terms used on the Scopus, Web of Science and Pubmed databases with the Boolean operator “AND”. The results of the last ten years of research were 146 studies; of these, 19 publications were included for this review. The distalization movement is possible with invisible masks alone, but the risk of losing anchorage in the anterior sectors is very probable. The stability of the results and the reduction of unwanted effects can be guaranteed by the use of skeletal anchoring devices and interproximal enamel reduction (IPR), with which compensations are obtained to reduce the initial overjet. Temporary anchorage devices (TADs) can be used to manage posterior anchorage after distalization of maxillary molars with aligners. This hybrid approach has demonstrated the greatest orthodontic success. TADs are useful aids to provide direct and indirect skeletal anchorage. The opposite effect must be considered when planning dental distalization, especially of the molars, in patients with large overjet, and corrective measures or the use of auxiliaries may be necessary to prevent midcourse corrections. This systematic review provides a critical evidence-based assessment of the predictability of dental distalization with CAs, an ever-evolving orthodontic techniqu

Orthodontic Relapse after Fixed or Removable Retention Devices: A Systematic Review

Retention constitutes a fundamental phase of orthodontic treatment, of which the patient must be made aware from the outset. Retention, which can be fixed or movable, has the task of maintaining over time and stabilising the results obtained during treatment. This study assessed the efficacy of using removable restraints versus fixed solutions for maintaining long-term outcomes. A comprehensive search across major databases—Pubmed, Web of Science, Scopus—used ‘relapse’ and ‘orthodontic’ as keywords to gather articles on relapse discussions. The primary focus was relapsed cases in post-fixed orthodontic therapy. Both fixed and removable retainer systems prove effective in preserving orthodontic achievements. While fixed devices require regular wire integrity checks, mobile devices require patient compliance, proper usage, and a recommended wear time. Studies indicate that fixed retainers are generally successful, with relapse rates varying based on the retainer type. Full-time use of removable devices surpasses night-only wear. Vacuum-formed and Hawley retainers offer similar effectiveness. Fixed retainers excel in long-term alignment stability, whereas removable ones have higher failure rates yet remain beneficial

Transorbital Ultrasound for Morphological and Haemodynamical Assessment of Optic Nerve in Multiple Sclerosis

Background and aims: Changes of the optic nerve (ON) reflect the overall pathology in multiple sclerosis (MS). Transorbital ultrasonography (TOUS) is a promising tool for detecting ON changes after exposure to optic neuritis. We aimed to explore ON haemodynamic in addition to morphological changes in a sample of MS patients. Methods: Sixty-seven MS patients (Thompson diagnostic criteria) were included in this preliminary study: 53 women and 14 men aged 41.6 (11.3) and 40.1 (11.0) (p=ns) years. EDSS score was 0-2.5 in 47 (70.1%) and >2.5 in 20 (14.9%) subjects. ANCOVA was used to investigate the association between US morphological (ON diameter (OND) at 3 and 5 mm from papilla, ON sheath diameter (ONSD) at 3 mm from papilla and myelination index (MI) ratio), a history of optic neuritis, controlling for sex and EDSS. Results: Out of 134 eyes no history of optic neuritis was recorded in 89 (66.4%), while at least 1 episode was recorded for 45 (33.6%). A higher proportion of affected eyes among women (86.4%) than men (13.6%) was observed (p=ns). OND – at 5 mm from papilla especially - and ONSD at 3 mm were significantly reduced in ONs with optic neuritis. MI ratios were higher in affected vs unaffected eyes. Mean ON diameters were lower in patients with higher EDSS score, irrespective of history optic neuritis. Mean flow velocity was reduced in affected eyes for all principal arteries explored. Conclusion: TOUS and Doppler US examination can detect ON changes in MS, showing potential for prognostic marker

Transorbital Ultrasonography and Doppler Ultrasound to investigate Optic Nerves in Multiple Sclerosis

Introduction: Changes of the optic nerve (ON) reflect the overall pathology in multiple sclerosis (MS). Transorbital ultrasonogra- phy (TOUS) is currently gaining interest as a promising tool for detecting ON changes after exposure to optic neuritis. We aimed to explore both ON morphological and haemodynamic changes in a sample of MS patients. Objectives/Aims: Morphological changes in the optic nerve may potentially reflect different stages of disease in multiple sclerosis (MS) patients. In this study we aimed to explore whether tran- sorbital ultrasonography and doppler ultrasound can detect mor- phological and haemodynamic changes in a sample of MS patients. Methods: 98 subjects (27 men and 71 women, F:M=2.6) with a diagnosis of MS according to McDonald criteria, aged 48.0 (14.0) and 45.0 (12.0) (p=ns) years, were enrolled. EDSS score was 0-2.5 in 63 (64.3%) and >2.5 in 35 (35.7%) subjects. Morphometric (ON diameters) and haemodynamic (from ophthal- mic artery, OA, central retinal artery, CRA, posterior ciliary arter- ies, PCA) features were computed for affected (AE) vs. non affected (nAE) eyes. Results: A history of ON (ON+) was detected in 55 (56.1%) patients, 11 (20.0%) men and 44 (80.0%) women (p=0.058). ON+ was associated with lower EDSS scores (76.1% with EDSS 0-2.5 vs. 23.6% >2.5, p=0.006, p-trend=0.005) and although not significant with younger age (<50 years at study time). For the study population, 192 (98.0%) eyes could be investigated, 67 (34.9%) with (AE) and 125 (65.1%) without past history of docu- mented inflammation (nAE). Overall ON diameter at 3 mm (OND3), and ON sheath diameters at 3 (ONSD3) and 5 (ONSD5) mm from papilla did not differ in patients with or without a history of ON, but tended to be smaller in AE. No difference was observed for the myelination index ratio. A tendency for lower mean flow velocities for OA in AE vs. nAE was detected (p=0.070), but not for CRA and PCA. Conclusion: Transorbital ultrasonography and doppler ultrasound methods can be applied to MS patients potentially indicating loss of optic nerve volume in association to past history of ON. A larger sample size is needed for confirmatory findings

Bedsores successfully treated with topical phenytoin

Phenytoin is normally used in epilepsy treatment. One of the side effect affecting a significative part of the treated patients is the gingival overgrowth. It could surely be a correlation between this stimulatory effect and the assessment of phenytoin in wound healing. In fact, some studies of the literature have shown that topical phenytoin promotes healing of traumatic wounds, burns and ulcers by decubitus or stasis (diabetic or venous) and we emphasize, in vitiligo, a particular attention into repigmentation. The related mechanism of action seems to be multifactorial. In the present paper topical phenytoin has been used as wound-healing agent in 19 documented cases of bedsores, divided in treated and placebo group. The used concentration of phenytoin was 5 mg/L dissolved in a water solution of 9 g NaCl /L (0.9% P/V of NaCl). Patches soaked with phenytoin solution were applied over the bedsores along 3 hours every 12 hours. Results showed that phenytoin treated patients healed their wounds significantly before (p<0.001) with respect to controls. (www.actabiomedica.it

Localized surface plasmon resonances in gold nano-patches on a gallium nitride substrate

In this paper we describe the design, fabrication and characterization of gold nano-patches, deposited on gallium nitride substrate, acting as optical nanoantennas able to efficiently localize the electric field at the metal-dielectric interface. We analyse the performance of the proposed device, evaluating the transmission and the electric field localization by means of a three-dimensional finite difference time domain (FDTD) method. We detail the fabrication protocol and show the morphological characterization. We also investigate the near-field optical transmission by means of scanning near-field optical microscope measurements, which reveal the excitation of a localized surface plasmon resonance at a wavelength of 633 nm, as expected by the FDTD calculations. Such results highlight how the final device can pave the way for the realization of a single optical platform where the active material and the metal nanostructures are integrated together on the same chip