Management of the Sequelae of a Sport-Related Traumatic Dental Injury Using Ultrasound Examination in the Diagnosis and Follow-Up

About a quarter of all oral pathologies involving the oral cavity and dental apparatus are traumatic injuries, and a substantial number of these cases are the result of sports injuries affecting adolescents and young adults. Here, we report the case of a 25-year-old healthy female referred to the department of Endodontics for the evaluation and management of teeth 1.2 and 1.1 because of a chronic apical abscess in an area involved in a sport-related dental trauma in the past. A multi-modular diagnostic assessment, comprising conventional periapical radiographs, CBCT imaging, ultrasound, and histopathologic examination, led to a final diagnosis of an apical granulomatous lesion connected to both teeth, and an associated sinus tract. During the follow-up period of three years, the patient was reviewed twice a year and showed progressive healing of the bone and absence of the sinus tract. The present report shows the challenges of diagnosing complications arising from past dental trauma. Furthermore, it is the first documented traumatic case where ultrasound examination was fruitfully used. Emphasis should be put on introducing diagnostic ultrasound for the management of both apical periodontitis and the related sinus tract

Combined Management of Apical Root Fracture and Avulsion of Two Maxillary Permanent Central Incisors: A Case Report

As a result of a skiing accident, a ten-year-old girl suffered combined injuries to both maxillary central incisor teeth (#1.1 and #2.1). The injuries were uncomplicated crown fractures, apical horizontal root fractures, and a severe extrusive luxation of the coronal segments of the teeth. Her mother repositioned the teeth immediately, resulting in good initial healing. Nine months later, the patient was referred to a specialist to manage the endodontic consequences of the trauma. The apexification treatment of the fractured roots, using a preformed apical barrier technique with bioactive cement, was the treatment of choice, administered to both the avulsed roots at two separate recall visits. The best option for managing the fractured apical segments was to continue with the follow-up, which was conducted to assess the overall case at 30 months. The fractured apexes remained normally positioned inside the socket and were asymptomatic (as they presumably maintained a physiological vascular-nerve supply and, consequently, their vitality), while the apexification treatment led to the healing of the periodontal tissues and to hard tissue formation in the area of the interrupted roots in the avulsed portion of the teeth. The management of traumatic injuries in teeth often requires multiple treatment approaches, because these injuries rarely represent one single type of trauma

Periapical status in patients affected by osteoporosis: A retrospective clinical study

Objectives: To assess the periapical status in patients with osteoporosis (OP) treated with denosumab (D), bisphosphonates (BPs), or not on medication, and to understand if these conditions influence the prevalence and the progression of apical periodontitis (AP).Material and Methods: Seventy-six patients with OP alone or treated with D, or BPs, formed the study group (O), and those from 76 patients matched for age and sex, without diseases, and not taking medications, constituted the control (C) in this retrospective case-control study. The data from the complete clinical and radiographic examination, medical history, decayed, missing, and filled teeth (DMFT), and periapical index score (PAI) were recorded for each patient. Wilcoxon rank test, chi(2), and Student's t test were used as appropriate.Results: The prevalence of AP was similar in O and C. Furthermore, AP was significantly more frequent in root canal-treated teeth in O patients (p = .03).Conclusions: OP does not appear to be associated with the development of AP. Moreover, the increased prevalence of AP in root canal-treated teeth in O patients highlights a possible relationship between the healing dynamics of the disease post-therapy and the patients' medication. A larger sample is needed to confirm these findings

Zebrafish Tric-b is required for skeletal development and bone cells differentiation

IntroductionTrimeric intracellular potassium channels TRIC-A and -B are endoplasmic reticulum (ER) integral membrane proteins, involved in the regulation of calcium release mediated by ryanodine (RyRs) and inositol 1,4,5-trisphosphate (IP3Rs) receptors, respectively. While TRIC-A is mainly expressed in excitable cells, TRIC-B is ubiquitously distributed at moderate level. TRIC-B deficiency causes a dysregulation of calcium flux from the ER, which impacts on multiple collagen specific chaperones and modifying enzymatic activity, leading to a rare form of osteogenesis imperfecta (OI Type XIV). The relevance of TRIC-B on cell homeostasis and the molecular mechanism behind the disease are still unknown.ResultsIn this study, we exploited zebrafish to elucidate the role of TRIC-B in skeletal tissue. We demonstrated, for the first time, that tmem38a and tmem38b genes encoding Tric-a and -b, respectively are expressed at early developmental stages in zebrafish, but only the latter has a maternal expression. Two zebrafish mutants for tmem38b were generated by CRISPR/Cas9, one carrying an out of frame mutation introducing a premature stop codon (tmem38b-/-) and one with an in frame deletion that removes the highly conserved KEV domain (tmem38bΔ120-7/Δ120-7). In both models collagen type I is under-modified and partially intracellularly retained in the endoplasmic reticulum, as described in individuals affected by OI type XIV. Tmem38b-/- showed a mild skeletal phenotype at the late larval and juvenile stages of development whereas tmem38bΔ120-7/Δ120-7 bone outcome was limited to a reduced vertebral length at 21 dpf. A caudal fin regeneration study pointed towards impaired activity of osteoblasts and osteoclasts associated with mineralization impairment.DiscussionOur data support the requirement of Tric-b during early development and for bone cell differentiation

Effect of RNS60 in amyotrophic lateral sclerosis: a phase II multicentre, randomized, double-blind, placebo-controlled trial

Background and purpose Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 is an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS and other neurodegenerative diseases. Its administration has been safe and well tolerated in ALS subjects in previous early phase trials. Methods This was a phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial. Participants diagnosed with definite, probable or probable laboratory-supported ALS were assigned to receive RNS60 or placebo administered for 24 weeks intravenously (375 ml) once a week and via nebulization (4 ml/day) on non-infusion days, followed by an additional 24 weeks off-treatment. The primary objective was to measure the effects of RNS60 treatment on selected biomarkers of inflammation and neurodegeneration in peripheral blood. Secondary objectives were to measure the effect of RNS60 on functional impairment (ALS Functional Rating Scale-Revised), a measure of self-sufficiency, respiratory function (forced vital capacity, FVC), quality of life (ALS Assessment Questionnaire-40, ALSAQ-40) and survival. Tolerability and safety were assessed. Results Seventy-four participants were assigned to RNS60 and 73 to placebo. Assessed biomarkers did not differ between arms. The mean rate of decline in FVC and the eating and drinking domain of ALSAQ-40 was slower in the RNS60 arm (FVC, difference 0.41 per week, standard error 0.16, p = 0.0101; ALSAQ-40, difference -0.19 per week, standard error 0.10, p = 0.0319). Adverse events were similar in the two arms. In a post hoc analysis, neurofilament light chain increased over time in bulbar onset placebo participants whilst remaining stable in those treated with RNS60. Conclusions The positive effects of RNS60 on selected measures of respiratory and bulbar function warrant further investigation

Dietary phosphorus : effects on skeletal development and mineralisation in zebrafish (Danio rerio)

Il fosforo è un macronutriente essenziale per diversi processi fisiologici, tra cui la mineralizzazione dello scheletro, e deve essere introdotto tramite l’alimentazione. È necessario assumere adeguati livelli di fosforo tramite l’alimentazione, per prevenire gli effetti correlati sia alla carenza, ovvero ritardo della crescita, ipomineralizzazione e deformità ossee, sia all'eccesso di fosforo, ovvero calcificazione dei tessuti molli e ipermineralizzazione ossea. Lo scopo di questa tesi è analizzare che conseguenze hanno diversi apporti di fosforo sullo scheletro attraverso l’alimentazione, utilizzando lo zebrafish come organismo modello. Gli obiettivi sono i) ottenere maggiori informazioni sui meccanismi alla base dell'ipo- e dell'ipermineralizzazione ossea, dovuti sia all'assunzione inadeguata di fosforo, sia a condizioni di malattia, e ii) chiarire entrambi i processi di formazione e mineralizzazione ossea. La morfologia e la mineralizzazione di diverse strutture dello scheletro di zebrafish sono analizzate utilizzando un'ampia gamma di tecniche complementari, che vanno da procedure istologiche a diverse tecniche radiografiche, analisi molecolari e test meccanici. Il primo importante risultato di questa tesi è la dimostrazione che la formazione di osso e la sua mineralizzazione sono processi indipendenti. Quando zebrafish è sottoposto ad un apporto ridotto di fosforo, la deposizione di matrice ossea non subisce alcun effetto. Anzi, la formazione di nuova matrice ossea è particolarmente stimolata in queste condizioni e avviene senza la sua conseguente mineralizzazione. Tale aumento della produzione di osso non porta allo sviluppo di malformazioni scheletriche in zebrafish. Al contrario, l'aumento dell'apporto nutrizionale di fosforo causa ipermineralizzazione e aumentata rigidità ossea, favorendo la fusione delle vertebre. È interessante notare come la grande quantità di matrice ossea non mineralizzata, prodotta in condizioni di ridotto apporto di fosforo, mineralizza non appena viene fornito fosforo in quantità sufficienti tramite l’alimentazione. Queste strutture ossee appaiono normali, ma la mineralizzazione tardiva di tali strutture ha come risultato un notevole aumento del volume osseo. Di conseguenza, si può dedurre che è possibile aumentare il volume delle ossa in zebrafish, stimolando prima la formazione di matrice ossea in condizioni di ridotto apporto di fosforo, e successivamente inducendone la mineralizzazione fornendo adeguati livelli di fosforo con l’alimentazione. In condizioni di ridotto apporto di fosforo, le ossa di zebrafish hanno anche un ridotto contenuto di minerale, caratteristica che ne migliora le proprietà biomeccaniche, aumentandone la resistenza e riducendone la rigidità. Questo approccio ha rivelato risultati promettenti nel moderare, sebbene in modo parziale, l'eccessiva mineralizzazione delle ossa che caratterizza l'osteogenesi imperfetta, una rara malattia genetica che causa fragilità e gravi deformità ossee. Il ridotto apporto di fosforo tramite l’alimentazione nel modello zebrafish chiamato Chihuahua, un valido modello per lo studio dell’osteogenesi imperfetta, ha dimostrato risultati incoraggianti nel modulare parzialmente il grave fenotipo osseo della malattia. Il nuovo modello zebrafish presentato in questa tesi è utile sia per chiarire gli effetti dei diversi apporti di fosforo sullo sviluppo osseo, sia per comprendere meglio la relazione tra formazione di matrice ossea e mineralizzazione ossea. Inoltre, l’evidenza sperimentale che lega il ridotto apporto di fosforo con la migliorata qualità dell’osso rappresenta un nuovo e promettente approccio per il trattamento di patologie caratterizzate da ipermineralizzazione ossea e/o riduzione del volume osseo. Inoltre, l'alternanza tra ridotto e aumentato apporto di fosforo può contribuire a contrastare la perdita di volume osseo dovuta all'invecchiamento o legata all’osteoporosi.Phosphorus (P) is a dietary macronutrient essential for several physiological processes. It participates in cellular metabolism and cell signalling, it is a constituent of phospholipids, of nuclei acids and of highly active intracellular compounds such as ATP. In vertebrates, P together with calcium is crucial for mineralisation of the skeleton. Adequate dietary P levels are required to prevent P deficiency- related effects, i.e. growth retardation, osteomalacia and bone deformities, as well as P-excess- related consequences, i.e. soft tissue calcification and bone hypermineralisation. The present thesis examines the effects of different dietary P levels on the skeleton using zebrafish as a model organism in skeletal research. The aims are i) to obtain insights into the mechanisms underlying osteomalacia and excess mineralisation, related both to inadequate P intake and to disease conditions, and ii) to better elucidate the processes of bone formation and mineralisation. The zebrafish skeletal elements, mainly the vertebral column, but also the dermal fin rays and the dentition, are analysed using a wide range of complementary techniques, ranging from histological procedures to different radiographic techniques, molecular analysis and mechanical testing. The first major finding of this thesis is that bone formation and bone mineralisation are uncoupled processes. When treating zebrafish with a reduced dietary P supply, bone matrix deposition, i.e. bone formation, continues uninterrupted. New bone matrix is formed, simply this bone does not mineralise due to the lack of P. The deposition of new bone matrix is even further stimulated under low P conditions. The increased production of bone matrix does not lead to the development of skeletal malformations in zebrafish. Conversely, increased dietary P supply leads to bone hypermineralisation, increases bone stiffness and promotes fusion of vertebral bodies. Interestingly, the large amount of non-mineralised bone matrix produced under low P conditions resumes mineralisation as soon as sufficient P is provided with the diet. These late mineralised bone structures appear normal, but the volume of the newly mineralised bone is dramatically increased. It is thus possible to increase the bone volume in zebrafish, first by stimulating bone matrix formation under low P conditions, and subsequently inducing the mineralisation of the newly formed bone by providing adequate dietary P. The low dietary P conditions also reduce the mineral content of the bone already present in zebrafish, enhancing its biomechanical properties by increasing toughness and reducing stiffness. This approach has been applied to partially rescue the bone hypermineralisation of osteogenesis imperfecta, a rare bone disorder mainly characterised by bone fragility and severe bone deformities. In the osteogenesis imperfecta mutant zebrafish called Chihuahua, the data obtained from the reduced dietary P treatment suggest a reduction in the mineral content of bone, resulting in a partial improvement of the severe bone phenotype typical of the disease. The low dietary P zebrafish model presented here allows to elucidate the effects of dietary P levels on bone development and to better understand the relationship between bone formation and bone mineralisation. Moreover, the experimental evidence linking dietary low P levels with bone quality improvement, represents a promising novel approach for the treatment of disease conditions characterised by bone hypermineralisation and bone loss. Furthermore, the alternation of low dietary P/sufficient dietary P can possibly contribute to reverse bone loss due to aging or osteoporosis conditions

Scrivere un “noir intercuturale”. Conversazione con Andrea Cotti

Andrea Cotti è scrittore e sceneggiatore. Ha scritto narrativa per ragazzi (Francesco vola) e poesie (Da quale fuoco), ma ha una particolare passione per il giallo (menzioniamo, tra gli altri, Un gioco da ragazze, adattato anche in forma cinematografica), che lo porta ad essere uno degli sceneggiatori delle serie L’ispettore Coliandro e Squadra Antimafia. È autore della serie dedicata al detective italo-cinese Luca Wu, composta ad oggi da un racconto, Bologna dall’alto è bellissima (2016) e due romanzi editi da Rizzoli, Il cinese (2018) e L’impero di mezzo (2021). Con Silvia Baroni dialoga sulla costruzione del detective interculturale Luca Wu e sul noir come mezzo per indagare la realtà

Combined Management of Apical Root Fracture and Avulsion of Two Maxillary Permanent Central Incisors: A Case Report

As a result of a skiing accident, a ten-year-old girl suffered combined injuries to both maxillary central incisor teeth (#1.1 and #2.1). The injuries were uncomplicated crown fractures, apical horizontal root fractures, and a severe extrusive luxation of the coronal segments of the teeth. Her mother repositioned the teeth immediately, resulting in good initial healing. Nine months later, the patient was referred to a specialist to manage the endodontic consequences of the trauma. The apexification treatment of the fractured roots, using a preformed apical barrier technique with bioactive cement, was the treatment of choice, administered to both the avulsed roots at two separate recall visits. The best option for managing the fractured apical segments was to continue with the follow-up, which was conducted to assess the overall case at 30 months. The fractured apexes remained normally positioned inside the socket and were asymptomatic (as they presumably maintained a physiological vascular-nerve supply and, consequently, their vitality), while the apexification treatment led to the healing of the periodontal tissues and to hard tissue formation in the area of the interrupted roots in the avulsed portion of the teeth. The management of traumatic injuries in teeth often requires multiple treatment approaches, because these injuries rarely represent one single type of trauma