Subcutaneous emphysema during root canal therapy: endodontic accident by sodium hypoclorite

Cervicofacial subcutaneous emphysema is defined as the abnormal introduction of air in the subcutaneous tissues of the head and neck. It is mainly caused by trauma, head and neck surgery, general anesthesia, and coughing or habitual performance of Valsalva manoeuvre. The occurrence of subcutaneous emphysema after dental treatment is rare, and diffusion of gas into the mediastinum is much rarer, especially when the procedure is a nonsurgical treatment. Presented here is a case of subcutaneous emphysema that occurred after sodium hypochlorite irrigation during endodontic treatment, and the description of its etiologies and prevention during nonsurgical endodontic treatment. Endodontic success can be essentially achieved via good debridement of a root canal, and an ideal endodontic irrigant is effective in removing the smear layer, opening the dentinal tubules, and producing a clean surface for closer obturation

Jet-environment interplay in magnetized binary neutron star mergers

GRB 170817A, the first short gamma-ray burst (sGRB) to be detected in coincidence with a gravitational wave signal, demonstrated that merging binary neutron star (BNS) systems can power collimated ultra-relativistic jets and, in turn, produce sGRBs. Moreover, it revealed that sGRB jets possess an intrinsic angular structure that is imprinted in the observable prompt and afterglow emission. Advanced numerical simulations represent the leading approach to investigate the physical processes underlying the evolution of sGRB jets breaking out of post-merger environments, and thus connect the final angular structure and energetics with specific jet launching conditions. In a previous paper, we carried out the first three-dimensional (3D) special-relativistic hydrodynamic simulations of incipient (top-hat) sGRB jets propagating across the realistic environment resulting from a general-relativistic (GR) hydrodynamic BNS merger simulation. While the above work marked an important step toward a consistent end-to-end description of sGRB jets from BNS mergers, those simulations did not account for the presence of magnetic fields, which are expected to play a key role. Here, we overcome this limitation, reporting the first 3D special-relativistic magnetohydrodynamic (MHD) simulation of a magnetized (structured and rotating) sGRB jet piercing through a realistic magnetized post-merger environment, wherein the initial conditions of the latter are directly imported from the outcome of a previous GRMHD BNS merger simulation.Comment: 16 pages, 15 figures, accepted for publication in MNRA

Short gamma-ray burst jet propagation in binary neutron star merger environments

The multimessenger event GW170817/GRB 170817A confirmed that binary neutron star (BNS) mergers can produce short gamma-ray burst (SGRB) jets. This evidence promoted new investigations on the mechanisms through which a BNS merger remnant can launch such a powerful relativistic outflow and on the propagation of the latter across the surrounding post-merger environment. In particular, great strides have been made in jet propagation models, establishing connections between the initial jet launching conditions, including the incipient jet launching time (with respect to merger) and the injection parameters, and the observable SGRB prompt and afterglow emission. However, present semi-analytical models and numerical simulations (with one notable exception) adopt simple hand-made prescriptions to account for the post-merger environment, lacking a direct association with any specific merging BNS system. Here, we present the first three-dimensional relativistic hydrodynamics simulations of incipient SGRB jets propagating through a post-merger environment that is directly imported from the outcome of a previous general relativistic BNS merger simulation. Our results show that the evolution and final properties of the jet can be largely affected by the anisotropies and the deviations from axisymmetry and homologous expansion characterizing more realistic BNS merger environments. In addition, we find that the inclusion of the gravitational pull from the central compact object, often overlooked, can have a major impact. Finally, we consider different jet launching times referred to the same BNS merger model and discuss the consequences for the ultimate jet properties.Comment: 16 pages, 20 figure

Whole exome sequencing in an Italian family with isolated maxillary canine agenesis and canine eruption anomalies

Objective: The aim of this study was the clinical and molecular characterization of a family segregating a trait consisting of a phenotype specifically involving the maxillary canines, including agenesis, impaction and ectopic eruption, characterized by incomplete penetrance and variable expressivity. Design: Clinical standardized assessment of 14 family members and a whole-exome sequencing (WES) of three affected subjects were performed. WES data analyses (sequence alignment, variant calling, annotation and prioritization) were carried out using an in-house implemented pipeline. Variant filtering retained coding and splice-site high quality private and rare variants. Variant prioritization was performed taking into account both the disruptive impact and the biological relevance of individual variants and genes. Sanger sequencing was performed to validate the variants of interest and to carry out segregation analysis. Results: Prioritization of variants “by function” allowed the identification of multiple variants contributing to the trait, including two concomitant heterozygous variants in EDARADD (c.308C>T, p.Ser103Phe) and COL5A1 (c.1588G>A, p.Gly530Ser), specifically associated with a more severe phenotype (i.e. canine agenesis). Differently, heterozygous variants in genes encoding proteins with a role in the WNT pathway were shared by subjects showing a phenotype of impacted/ectopic erupted canines. Conclusions: This study characterized the genetic contribution underlying a complex trait consisting of isolated canine anomalies in a medium-sized family, highlighting the role of WNT and EDA cell signaling pathways in tooth development

Head and neck osteosarcoma—the ongoing challenge about reconstruction and dental rehabilitation

Head and Neck osteosarcoma is an uncommon disease. Hitherto, the treatment is surgical resection and survival is influenced by the presence of free margins. However, the dimension of the resection may represent a hurdle for an adequate Quality of Life (QOL). Maxillofacial district is a narrow space where the function, esthetics and patient’s relational skills fit together like the gears of a clock. The functional results depend on the type of reconstruction and prosthetic rehabilitation that are both important to guarantee a good aesthetic result and finally increase the patient’s self-esteem. This study aims to report our experience about head and neck (HN) osteosarcoma focusing the attention on reconstructive and dental-rehabilitative problems. It is a retrospective study all patients were surgically treated in our department. Subjects with histological diagnosis of HN osteosarcoma, treated between 2005 and 2017 were included. The demographic characteristics, surgical treatment, eventually secondary reconstruction and prosthetic rehabilitation, performed in the same department, have been collected. The QOL was assessed through the EORTC QLQ-H&N35 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35) questionnaire. Fifteen patients were enrolled, eight received a free flap microsurgical reconstruction. Dental rehabilitation was performed in five cases and a mobile prosthesis was always delivered. Eighteen implants were inserted in fibula bones for three patients; highly porous implants were use

General relativistic magnetohydrodynamic simulations of binary neutron star mergers forming a long-lived neutron star

Merging binary neutron stars (BNSs) represent the ultimate targets for multimessenger astronomy, being among the most promising sources of gravitational waves (GWs), and, at the same time, likely accompanied by a variety of electromagnetic counterparts across the entire spectrum, possibly including short gamma-ray bursts (SGRBs) and kilonova/macronova transients. Numerical relativity simulations play a central role in the study of these events. In particular, given the importance of magnetic fields, various aspects of this investigation require general relativistic magnetohydrodynamics (GRMHD). So far, most GRMHD simulations focused the attention on BNS mergers leading to the formation of a hypermassive neutron star (NS), which, in turn, collapses within few tens of ms into a black hole surrounded by an accretion disk. However, recent observations suggest that a significant fraction of these systems could form a long-lived NS remnant, which will either collapse on much longer time scales or remain indefinitely stable. Despite the profound implications for the evolution and the emission properties of the system, a detailed investigation of this alternative evolution channel is still missing. Here, we follow this direction and present a first detailed GRMHD study of BNS mergers forming a long-lived NS. We consider magnetized binaries with different mass ratios and equations of state and analyze the structure of the NS remnants, the rotation profiles, the accretion disks, the evolution and amplification of magnetic fields, and the ejection of matter. Moreover, we discuss the connection with the central engine of SGRBs and provide order-of-magnitude estimates for the kilonova/macronova signal. Finally, we study the GW emission, with particular attention to the post-merger phase

Mutations in KCNK4 that Affect Gating Cause a Recognizable Neurodevelopmental Syndrome

Aberrant activation or inhibition of potassium (K+) currents across the plasma membrane of cells has been causally linked to altered neurotransmission, cardiac arrhythmias, endocrine dysfunction, and (more rarely) perturbed developmental processes. The K+ channel subfamily K member 4 (KCNK4), also known as TRAAK (TWIK-related arachidonic acid-stimulated K+ channel), belongs to the mechano-gated ion channels of the TRAAK/TREK subfamily of two-pore-domain (K2P) K+ channels. While K2P channels are well known to contribute to the resting membrane potential and cellular excitability, their involvement in pathophysiological processes remains largely uncharacterized. We report that de novo missense mutations in KCNK4 cause a recognizable syndrome with a distinctive facial gestalt, for which we propose the acronym FHEIG (facial dysmorphism, hypertrichosis, epilepsy, intellectual disability/developmental delay, and gingival overgrowth). Patch-clamp analyses documented a significant gain of function of the identified KCNK4 channel mutants basally and impaired sensitivity to mechanical stimulation and arachidonic acid. Co-expression experiments indicated a dominant behavior of the disease-causing mutations. Molecular dynamics simulations consistently indicated that mutations favor sealing of the lateral intramembrane fenestration that has been proposed to negatively control K+ flow by allowing lipid access to the central cavity of the channel. Overall, our findings illustrate the pleiotropic effect of dysregulated KCNK4 function and provide support to the hypothesis of a gating mechanism based on the lateral fenestrations of K2P channels

Mutations impairing GSK3-mediated MAF phosphorylation cause cataract, deafness, intellectual disability, seizures, and a down syndrome-like facies

Transcription factors operate in developmental processes to mediate inductive events and cell competence, and perturbation of their function or regulation can dramatically affect morphogenesis, organogenesis, and growth. We report that a narrow spectrum of amino-acid substitutions within the transactivation domain of the v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF), a leucine zipper-containing transcription factor of the AP1 superfamily, profoundly affect development. Seven different de novo missense mutations involving conserved residues of the four GSK3 phosphorylation motifs were identified in eight unrelated individuals. The distinctive clinical phenotype, for which we propose the eponym Aymé-Gripp syndrome, is not limited to lens and eye defects as previously reported for MAF/Maf loss of function but includes sensorineural deafness, intellectual disability, seizures, brachycephaly, distinctive flat facial appearance, skeletal anomalies, mammary gland hypoplasia, and reduced growth. Disease-causing mutations were demonstrated to impair proper MAF phosphorylation, ubiquitination and proteasomal degradation, perturbed gene expression in primary skin fibroblasts, and induced neurodevelopmental defects in an in vivo model. Our findings nosologically and clinically delineate a previously poorly understood recognizable multisystem disorder, provide evidence for MAF governing a wider range of developmental programs than previously appreciated, and describe a novel instance of protein dosage effect severely perturbing developmen