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

Eyelid bags

Eyelid bags are considered a sign of ageing, but they often appear prematurely due to the variety of causes that favor them. This brief report describes the case of a patient who was referred to us for the correction of a second degree bilateral palpebral ptosis that the patient had suffered from for several years and that in recent months had worsened to the point of interfering with vision and who, aside from modest eyelid bags, presented a massive protrusion of "preocular" fatty tissue. Despite the indication of classic blepharoplasty through a lower lid incision and, therefore, the possibility of removing excess skin, the patient opted instead only for the removal of the bulging fat. The patient's postoperative results were normal and the patient was extremely satisfied with both the correction of the ptosis and the "rejuvenating" effect of removing the protruding orbital fat in the eyelid

Low-Level Light Therapy in Orthodontic Treatment: A Systematic Review

This current review aims to provide an overview of the most recent research from the last 10 years on the potential of low-level light therapy (LLLT) in the orthodontic field, particularly focusing on studies about tooth movement, root resorption, pain perception during treatment, and the stability of orthodontic miniscrews. “Low-level laser,” “orthodontic,” and “LLLT” were the search terms utilized on the databases Scopus, Web of Science, and PubMed, and the Boolean operator “AND” was utilized. Of the 974 studies found, 41 publications related to our topic were included in this review. Many authors agree that LLLT could trigger an enhanced biological reaction next to the tooth in the periodontium, promoting osteoblast proliferation and differentiation, while it could also have a positive impact on bone regeneration and on increasing the rate of tooth movement, enhancing the stability of miniscrews and minimizing the occurrence of root resorption. Regarding pain management during treatment studies, the results have been controversial. Conclusions: even though further studies are still needed, the use of LLLT can improve both clinical results and patient comfort during treatment by reducing treatment duration, improving clinical aspects, such as miniscrew stability, and minimizing root resorption. Further investigations are needed to assess whether LLLT offers any real benefits regarding pain relief

Simple Technique for Augmentation of the Facial Soft Tissue

Due to the request of numerous patients to improve the aspect of the perioral area in combination with other types of cosmetic and reconstructive surgery, we started to use autologous fillers. In fact, there are numerous potential fillers that can be utilized during various operations executed in many bodily areas, such as the breast, abdomen, and face. The muscular fascia as well as the dense connective tissue which the surgeon encounters in various bodily areas during some stages of the operation, in fact, can be removed and replaced both by themselves or superimposed in order to increase their thickness. The insertion of the grafts is carried out by using a needle, but other methods can also be used with the same success. The consistency of the area treated, after a few days of edema, is very similar to the host area, and the volume obtained remains uniform in time (our followup is after 24 months). The time utilized for the removal and the insertion in the chosen area was only a few minutes. The result was extremely satisfactory in all the 30 patients treated, and there was no complication or side effects