Minimally invasive orthodontics: elastodontic therapy in a growing patient affected by Dentinogenesis Imperfecta

AIM: The aim of the study was to report the use of an elastodontic therapy in a growing patient affected by Dentinogenesis Imperfecta, second class malocclusion, deep bite and lower arch crowding from the deciduous dentition to permanent one. CASE REPORT: At first, the 5-year-old patient was treated with an elastodontic device known as "Nite-Guide". When the patient was 7 years old, during her first permanent molars and incisors eruption and after optimal house-practices, an Occlus-o-Guide Series G was placed at night and on daylight (two hours a day) performing exercises aimed to activate facial muscles and facilitate the deep bite reopening. At 9 years of age, with totally deep bite resolution, she used the Occluso-Guide only at night to hold down previous results and follow patient's dental growth. At 11 years of age, after successful teeth switching, we prescribed an Occlus-o-Guide Series N, which is functional for permanent dentition and guaranteed an eruptive guide for last dental elements. CONCLUSIONS: This clinic case could be considered an example of approach for all those patients with systemic and/or dental diseases that do not allow adequate dental retention, which is necessary for most orthodontic appliances; elastodontic devices do not require adequate dental retention and define a minimum intervention on the surfaces of the teeth

Healing environment in pediatric dentistry: strategies adopted by “Sapienza” University of Rome

Children’s dental anxiety has been of great worry for many years and it is still a barrier for dental care. According to recent guidelines for oral health prevention in childhood, additional strategies for a preventive care should be applied for pediatric patients. So it’s important to encourage pediatric dentists to develop a “child-friendly” environment for treating children. Environmental elements that produce positive feelings can reduce anxiety. The analysis of environmental design and features applied in Pediatric Dentistry Unit, Department of Oral and Maxillo-facial sciences, Sapienza University of Rome, highlighted special attention to the aspects supporting sensory conditions (colors, light, spatial organization); reassurance strategies (decorations, dental team attire, drawings); anxiety control strategies (playing area, TV, comics, toys); behavioral management strategies (positive reinforcement, modeling); in-formation (brochures, posters)

Reticulon1-C modulates protein disulphide isomerase function

Endoplasmic reticulum (ER) is the primary site for the synthesis and folding of secreted and membrane-bound proteins. Accumulation of unfolded and misfolded proteins in ER underlies a wide range of human neurodegenerative disorders. Hence, molecules regulating the ER stress response represent potential candidates as drug targets for tackling these diseases. Protein disulphide isomerase (PDI) is a chaperone involved in ER stress pathway, its activity being an important cellular defense against protein misfolding. Here, we demonstrate that human neuroblastoma SH-SY5Y cells overexpressing the reticulon protein 1-C (RTN1-C) reticulon family member show a PDI punctuate subcellular distribution identified as ER vesicles. This represents an event associated with a significant increase of PDI enzymatic activity. We provide evidence that the modulation of PDI localization and activity does not only rely upon ER stress induction or upregulation of its synthesis, but tightly correlates to an alteration in its nitrosylation status. By using different RTN1-C mutants, we demonstrate that the observed effects depend on RTN1-C N-terminal region and on the integrity of the microtubule network. Overall, our results indicate that RTN1-C induces PDI redistribution in ER vesicles, and concomitantly modulates its activity by decreasing the levels of its S-nitrosylated form. Thus RTN1-C represents a promising candidate to modulate PDI function

Altered expression of antioxidant enzymes and autophagic proteins in transglutaminase 2 knockout mice

""Background. Transglutaminases (TGs) are ubiquitous calcium-dependent acyl-transferases, catalysing post-translational protein modifications. Among the family members, TG2 (or "tissue" transglutaminase) acts as a multifunctional protein regulating cell processes, including autophagy [1,2]. . TG2 is highly expressed in the nervous tissue and reportedly involved in neurodegenerative disorders [3]. Indeed, the pathophysiology of these diseases includes insoluble aggregate formation, and covalent cross-linking of pathogenic proteins by TG2 has been suggested. Another hallmark of neurodegeneration is dysregulated autophagy, thus making the role played by TG2 in this cellular process especially relevant. Interestingly, conditions promoting TG2 activity, such as low GTP and high calcium levels, associated with oxidative stress, occur in neurodegeneration. . The present study aims to clarify the role of TG2 in redox balance and autophagy. To this purpose, the expression levels of antioxidant enzymes and pro-autophagic proteins were investigated in various brain regions and liver of TG2-\\\/- mice. . . Materials and methods. Expression of antioxidant enzymes, namely superoxide dismutase 1 and 2 (SOD1, SOD2), catalase (CAT) and glutathione peroxidase 1 (GPX1), and autophagic proteins (Beclin1, LC3 and AMBRA1) were evaluated by Western blotting (WB) and immunohistochemistry in selected brain areas (neocortex, hippocampus, brainstem, and cerebellum) and liver of 12-month-old TG2-\\\/- and wild-type mice.. . Results. WB and immunohistochemical data reveal altered expression patterns of antioxidant enzymes in both liver and brain tissues. Of particular interest is the statistically significant decrease of CAT and SOD2 in the cerebellum and hippocampus of TG2-\\\/- mice, while unchanged levels of these proteins are detected in the neocortex and brainstem. In the knockout liver, even more dramatic reduction of CAT and SOD2 expression is found, while SOD1 is intriguingly upregulated. Concerning the effect of TG2 deletion on autophagy, Beclin1 is down-regulated in the neocortex and hippocampus of knockout mice.. . Conclusions. Overall, our data on TG2-\\\/- mice support the involvement of the transamidating enzyme in controlling redox balance of different organs, and in regulating autophagic flux [1-3]. The specific decrease in the peroxisomal enzyme CAT and in the mitochondrial protein SOD2 emphasizes the role of these organelles in oxidative stress management and their interplay in cell metabolism. Moreover, region-based differences in the effect of TG2 deletion may reflect multiple functions related to the organ, tissue and cell type.. "

AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1

Damaged mitochondria are eliminated by mitophagy, a selective form of autophagy whose dysfunction associates with neurodegenerative diseases. PINK1, PARKIN and p62/SQTMS1 have been shown to regulate mitophagy, leaving hitherto ill-defined the contribution by key players in 'general' autophagy. In basal conditions, a pool of AMBRA1 - an upstream autophagy regulator and a PARKIN interactor - is present at the mitochondria, where its pro-autophagic activity is inhibited by Bcl-2. Here we show that, upon mitophagy induction, AMBRA1 binds the autophagosome adapter LC3 through a LIR (LC3 interacting region) motif, this interaction being crucial for regulating both canonical PARKIN-dependent and -independent mitochondrial clearance. Moreover, forcing AMBRA1 localization to the outer mitochondrial membrane unleashes a massive PARKIN- and p62-independent but LC3-dependent mitophagy. These results highlight a novel role for AMBRA1 as a powerful mitophagy regulator, through both canonical or noncanonical pathways

New perspectives on the Italian instrumental music renaissance over the long nineteenth century

This commentary presents my submitted publications contextualised in a broader study on the resurgence of Italian instrumental music during the ‘long nineteenth century’. By exploring the socio-political and economic status of the country over the century, my research acknowledges the pivotal role played by the Risorgimento process in shaping the development of a modern Italian musical culture. The research draws upon previously unexamined primary sources, including letters, concert programs, reviews, and a wide range of secondary literature. The commentary begins with a broad introduction examining the historical background, aiming to demonstrate the intrinsic connection between the development of an instrumental musical culture in Italy and the corresponding intellectual and cultural advancements. The commentary then consolidates and develops the research presented in the publications to offer an analysis of prominent Italian cities (Rome, Naples, Bologna, Turin, Milan, and Florence) and their distinctive characteristics. I unveil the diverse responses of each centre (and therefore of different areas of the country) to the challenges posed by the prevailing influence of opera and the political and economic circumstances that allowed the resurgence of instrumental music. I highlight the establishment of pioneering concert and quartet societies in these locations, which served as catalysts for the flourishing of Italian instrumental music. Furthermore, I demonstrate how the reform of school education and conservatories played a crucial role in empowering a new generation of Italian musicians to reclaim and excel in this genre. I throw new light upon those notable Italian composers, particularly Giuseppe Martucci, who played a crucial role in establishing a new and distinct ‘non-operatic’ image within Italian music culture, with a consequent impact in shaping the perception and reception of Italian music on an international scale. The outcomes of this research establish a groundwork for future investigation aimed at offering a more comprehensive overview of instrumental music culture across the Italian peninsula

Fenretinide induces autophagic cell death in caspase-defective breast cancer cells

The elimination of tumor cells by apoptosis is the main mechanism of action of chemotherapeutic drugs. More recently, autophagic cell death has been shown to trigger a nonapoptotic cell death program in cancer cells displaying functional defects of caspases. Fenretinide (FenR), a synthetic derivative of retinoic acid, promotes growth inhibition and induces apoptosis in a wide range of tumor cell types. The present study was designed to evaluate the ability of fenretinide to induce caspase-independent cell death and to this aim we used the human mammary carcinoma cell line MCF-7, lacking functional caspase-3 activity. We demonstrated that in these cells fenretinide is able to trigger an autophagic cell death pathway. In particular we found that fenretinide treatment resulted in the increase in Beclin 1 expression, the conversion of the soluble form of LC3 to the autophagic vesicle-associated form LC3-II and its shift from diffuse to punctate staining and finally the increase in lysosomes/autophagosomes. By contrast, caspase-3 reconstituted MCF-7 cell line showed apoptotic cell death features in response to fenretinide treatment. These data strongly suggest that fenretinide does not invariably elicit an apoptotic response but it is able to induce autophagy when apoptotic pathway is deregulated. The understanding of the molecular mechanisms involved in fenretinide action is important for the future design of therapies employing this retinoid in breast cancer treatment

Apoptosome-deficient cells lose cytochrome c through proteasomal degradation but survive by autophagy-dependent glycolysis

Cytochrome c release from mitochondria promotes apoptosome formation and caspase activation. The question as to whether mitochondrial permeabilization kills cells via a caspase-independent pathway when caspase activation is prevented is still open. Here we report that proneural cells of embryonic origin, when induced to die but rescued by apoptosome inactivation are deprived of cytosolic cytochrome c through proteasomal degradation. We also show that, in this context, those cells keep generating ATP by glycolysis for a long period of time and that they keep their mitochondria in a depolarized state that can be reverted. Moreover, under these conditions, such apoptosome-deficient cells activate a Beclin 1-dependent autophagy pathway to sustain glycolytic-dependent ATP production. Our findings contribute to elucidating what the point-of-no-return in apoptosis is. They also help in clarifying the issue of survival of apoptosome-deficient proneural cells under stress conditions. Unraveling this issue could be highly relevant for pharmacological intervention and for therapies based on neural stem cell transfer in the treatment of neurological disorders

Neuropathology and Inflammatory Cell Characterization in 10 Autoptic COVID-19 Brains

COVID-19 presents with a wide range of clinical neurological manifestations. It has been recognized that SARS-CoV-2 infection affects both the central and peripheral nervous system, leading to smell and taste disturbances; acute ischemic and hemorrhagic cerebrovascular disease; encephalopathies and seizures; and causes most surviving patients to have long lasting neurological symptoms. Despite this, typical neuropathological features associated with the infection have still not been identified. Studies of post-mortem examinations of the cerebral cortex are obtained with difficulty due to laboratory safety concerns. In addition, they represent cases with different neurological symptoms, age or comorbidities, thus a larger number of brain autoptic data from multiple institutions would be crucial. Histopathological findings described here are aimed to increase the current knowledge on neuropathology of COVID-19 patients. We report post-mortem neuropathological findings of ten COVID-19 patients. A wide range of neuropathological lesions were seen. The cerebral cortex of all patients showed vascular changes, hyperemia of the meninges and perivascular inflammation in the cerebral parenchyma with hypoxic neuronal injury. Perivascular lymphocytic inflammation of predominantly CD8-positive T cells mixed with CD68-positive macrophages, targeting the disrupted vascular wall in the cerebral cortex, cerebellum and pons were seen. Our findings support recent reports highlighting a role of microvascular injury in COVID-19 neurological manifestations