Virtual Surgical Planning of Superior Orbital Rim Fractures in Calvarial and Maxillofacial Trauma.

BACKGROUND: Superior orbital rim fractures are challenging fractures as they often concomitantly occur with additional calvaria fractures. Virtual surgical planning (VSP) has been underutilized in this area of craniomaxillofacial trauma for reconstruction. PURPOSE: The purpose of this study is to qualitatively describe the use of VSP and anatomically perfected stereolithic models in treatment of superior orbital rim fractures in combined neurosurgery/oral and maxillofacial surgery cases. STUDY DESIGN, SETTING, SAMPLE: This study is a retrospective case series of subjects who were treated at the Massachusetts General Hospital (July 2022 to November 2022). Inclusion criteria include subjects who had both calvaria and maxillofacial injuries requiring concurrent operative intervention on their superior orbital rim fractures and the use of VSP. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: Not applicable. MAIN OUTCOME VARIABLE: The outcome variable of interest is the difference in the planned position of the orbital rim repair compared to the actual position achieved. COVARIATES: None. ANALYSES: Heat map analysis was used to compare the difference in the planned position versus the actual position achieved. RESULTS: There were six orbits (five subjects, mean age 33.8 ± 21.49 years) that met the criteria. The mean difference in planned versus actual orbital volume achieved was 2.52 ± 2.48 cm3. The superimposition of the postoperative scan to the planned simulation revealed 84% ± 3.27% of the voxel surface was within +2 and -2 millimeters of its planned position. CONCLUSION AND RELEVANCE: This study has demonstrated the use of VSP in combined neurosurgery and oral and maxillofacial surgery procedures in the fixation of superior orbital rim fractures. This case series highlights that the postoperative position achieved in the six orbits was within 84% of the planned position.

Traumatic and non-traumatic dental presentations to the paediatric emergency departments of two UK children's hospitals: A multi-centre evaluation.

BACKGROUND: Dental attendances to paediatric emergency departments (PEDs) represent suboptimal use of resources of an unknown scale. AIM: To evaluate dental attendances at two PEDs in the UK and compare traumatic dental injury (TDI) and non-traumatic dental conditions (NTDCs). DESIGN: Retrospective data were collected for a 12-month period including demographics, attendance pattern, assessment, and management. Maxillofacial conditions were excluded, and attendances were grouped as TDI and NTDC. RESULTS: Of 667 attendances, 35.1% (n = 234) were TDI and 64.9% (n = 433) NTDC. Nineteen children reattended. Proportionately, more TDI attenders were male, White British, of lower mean age, and resided in less deprived areas than NTDCs. Over half (52.3%, n = 339) of attendees resided in the 10% most deprived UK areas. Saturday and Monday were modal attendance days; attendance peaked in summer. Over half (56.4%, n = 376) attended out of hours. A majority (74.8%, n = 499) self-referred and half accessed no other service prior to PED attendance. No PED dental input was received for 38.7% (n = 258), and dental treatment was received for 12.4% (n = 83). Antibiotics were provided for 42.1% (n = 281), and 15.4% (n = 103) were admitted. CONCLUSION: Dental abscesses and toothache accounted for half of attendances, many of these children may be managed in primary care. Improved signposting to alternative dental services for non-urgent conditions may better allocate resources to those with urgent need.

Modelling the non-local thermodynamic equilibrium spectra of silylene (SiH2).

This paper sets out a robust methodology for modelling spectra of polyatomic molecules produced in reactive or dissociative environments, with vibrational populations outside local thermal equilibrium (LTE). The methodology is based on accurate, extensive ro-vibrational line lists containing transitions with high vibrational excitations and relies on the detailed ro-vibrational assignments. The developed methodology is applied to model non-LTE IR and visible spectra of silylene (SiH2) produced in a decomposition of disilane (Si2H6), a reaction of technological importance. Two approaches for non-LTE vibrational populations of the product SiH2 are introduced: a simplistic 1D approach based on the Harmonic approximation and a full 3D model incorporating accurate vibrational wavefunctions of SiH2 computed variationally with the TROVE (Theoretical ROVibrational Energy) program. We show how their non-LTE spectral signatures can be used to trace different reaction channels of molecular dissociations.

Theoretical rovibronic spectroscopy of the calcium monohydroxide radical (CaOH).

The rovibronic (rotation-vibration-electronic) spectrum of the calcium monohydroxide radical (CaOH) is of interest to studies of exoplanet atmospheres and ultracold molecules. Here, we theoretically investigate the Ã2Π-X̃2Σ+ band system of CaOH using high-level ab initio theory and variational nuclear motion calculations. New potential energy surfaces (PESs) are constructed for the X̃2Σ+ and Ã2Π electronic states along with Ã-X̃ transition dipole moment surfaces (DMSs). For the ground X̃2Σ+ state, a published high-level ab initio PES is empirically refined to all available experimental rovibrational energy levels up to J = 15.5, reproducing the observed term values with a root-mean-square error of 0.06 cm-1. Large-scale multireference configuration interaction calculations using quintuple-zeta quality basis sets are employed to generate the Ã2Π state PESs and Ã-X̃ DMSs. Variational calculations consider both Renner-Teller and spin-orbit coupling effects, which are essential for a correct description of the spectrum of CaOH. Computed rovibronic energy levels of the Ã2Π state, line list calculations up to J = 125.5, and an analysis of Renner-Teller splittings in the ν2 bending mode of CaOH are discussed.

Whole-exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene.

As subsets of pheochromocytomas (PCCs) lack a defined molecular etiology, we sought to characterize the mutational landscape of PCCs to identify novel gene candidates involved in disease development. A discovery cohort of 15 PCCs wild type for mutations in PCC susceptibility genes underwent whole-exome sequencing, and an additional 83 PCCs served as a verification cohort for targeted sequencing of candidate mutations. A low rate of nonsilent single nucleotide variants (SNVs) was detected (6.1/sample). Somatic HRAS and EPAS1 mutations were observed in one case each, whereas the remaining 13 cases did not exhibit variants in established PCC genes. SNVs aggregated in apoptosis-related pathways, and mutations in COSMIC genes not previously reported in PCCs included ZAN, MITF, WDTC1, and CAMTA1. Two somatic mutations and one constitutional variant in the well-established cancer gene lysine (K)-specific methyltransferase 2D (KMT2D, MLL2) were discovered in one sample each, prompting KMT2D screening using focused exome-sequencing in the verification cohort. An additional 11 PCCs displayed KMT2D variants, of which two were recurrent. In total, missense KMT2D variants were found in 14 (11 somatic, two constitutional, one undetermined) of 99 PCCs (14%). Five cases displayed somatic mutations in the functional FYR/SET domains of KMT2D, constituting 36% of all KMT2D-mutated PCCs. KMT2D expression was upregulated in PCCs compared to normal adrenals, and KMT2D overexpression positively affected cell migration in a PCC cell line. We conclude that KMT2D represents a recurrently mutated gene with potential implication for PCC development.

Are cleft palate fistulae a cause of dental decay?

AIM: To investigate a possible correlation between fistula and dental decay in children at 5 years of age from a single-surgeon series of cleft palate repairs. METHODS: Retrospective review of data over a 9-year period between 2003 and 2011 of cleft palate repairs performed by the senior author at Birmingham Children's Hospital, U.K. Data collected on age, sex, age at repair, presence of fistula, and number of decayed, missing, or filled primary teeth (i.e., decayed, missing, and filled teeth score) at age 5 years. RESULTS: The overall fistula rate for this patient population was 24.1%. Fistulae were more common in the more severe forms of cleft type, as was frequency of dental decay. Comparison of fistula versus nonfistula groups showed a higher rate of dental decay (40%) in the fistula group, compared with only 20% in the nonfistula group (P = .036). CONCLUSION: A positive association was established between dental decay and the presence of a fistula. Although not proven as causative, possible reasons for this include nasal mucus retaining sugary food in the mouth and an overall prolonged food-clearance time. The known association between severity of cleft and an increased likelihood of a fistula and severity of cleft and increased dental decay were again demonstrated but were not found to be the exclusive explanation for the new finding of an association between fistulae and higher dental decay rates.

Assessment of the US EPA's determination of the role for CO2 capture and storage in new fossil fuel-fired power plants.

On September 20, 2013, the US Environmental and Protection Agency (EPA) proposed a revised rule for "Standards of Performance for Greenhouse Gas Emissions from New Stationary Sources: Electric Utility Generating Units". These performance standards set limits on the amount of carbon dioxide (CO2) that can be emitted per megawatt-hour (MWh) of electricity generation from new coal-fired and natural gas-fired power plants built in the US. These limits were based on determinations of "best system of emission reduction (BSER) adequately demonstrated". Central in this determination was evaluating whether Carbon Dioxide Capture and Storage (CCS) qualified as BSER. The proposed rule states that CCS qualifies as BSER for coal-fired generation but not for natural gas-fired generation. In this paper, we assess the EPA's analysis that resulted in this determination. We are not trying to judge what the absolute criteria are for CCS as the BSER but only the relative differences as related to coal- vs natural gas-fired technologies. We conclude that there are not enough differences between "base load" coal-fired and natural gas-fired power plants to justify the EPA's determination that CCS is the BSER for coal-fired power plants but not for natural gas-fired power plants.

Hospital admissions for dental treatment among children with cleft lip and/or palate born between 1997 and 2003: an analysis of Hospital Episode Statistics in England.

BACKGROUND: Children with clefts have an increased tendency for dental anomalies and caries. AIM: To determine the pattern of hospital admissions for dental treatment during primary dentition among children with clefts. DESIGN: Cohort study based on Hospital Episode Statistics, an administrative database of all admissions to National Health Service hospitals in England. Patients born alive between 1997 and 2003 who had both a cleft diagnosis and cleft repair were included. The number of hospital admissions for surgical removal of teeth, simple extraction of teeth, and restoration of teeth before the age of seven was examined. RESULTS: Eight hundred and fifty-eight hospital admissions for dental treatment among 6551 children (<7 year) with a cleft were identified. 66.4% of admissions were primarily for caries and 95.6% involved extractions. 11.4% of children had at least one admission for dental treatment. The presence of additional anomalies, having a more severe cleft type, and living in relatively deprived areas increased the risk of hospital admission. CONCLUSIONS: Factors increasing the risk of hospital admission among cleft children should be taken into account when planning services. Efforts to reduce the number of hospital admissions should be focused on disease prevention, particularly among those most at risk of caries.

Fluorescence and immune-cell infiltration of nonneoplastic, postbrachytherapy brain tissue in 5-ALA-guided resection of recurrent anaplastic meningioma: illustrative case.

BACKGROUND: 5-Aminolevulinic acid (5-ALA) fluorescence-guided surgery is a well-established technique for resecting high-grade gliomas. However, its application in meningiomas, especially those previously treated with radiation therapy, remains under investigation. OBSERVATIONS: A 48-year-old female with recurrent anaplastic meningioma, World Health Organization grade 3, underwent a right-sided craniotomy using off-label 5-ALA as a surgical adjunct. The patient had previously undergone brachytherapy seed implantation (20 × cesium 131) for tumor management. During the surgery, a large fluorescent tumor mass adjacent to the brachytherapy-treated area was resected, and the prior brachytherapy seeds were removed. Interestingly, the surrounding brain tissue in the irradiated area showed robust 5-ALA fluorescence. Pathological examination confirmed that the fluorescent brain tissue was nonneoplastic and associated with lymphocyte and macrophage infiltration. LESSONS: This case report presents unique 5-ALA fluorescence in nonneoplastic tissue following brachytherapy, which was found during the resection of recurrent anaplastic meningioma. This phenomenon may reflect an intricate interplay among radiation therapy, immune cells, the tumor microenvironment, and 5-ALA metabolism. Given that false-positive findings in fluorescence-guided surgery can lead to unnecessary tissue resection and increased surgical morbidity, further research is warranted to elucidate the mechanisms underlying this phenomenon and its implications for meningioma surgery.

Genetic characterization and mutational profiling of foramen magnum meningiomas: a multi-institutional study.

OBJECTIVE: Foramen magnum (FM) meningiomas pose significant surgical challenges and have high morbidity and mortality rates. This study aimed to investigate the distribution of clinically actionable mutations in FM meningiomas and identify clinical characteristics associated with specific mutational profiles. METHODS: The authors conducted targeted next-generation sequencing of 62 FM meningiomas from three international institutions, covering all relevant meningioma genes (AKT1, KLF4, NF2, POLR2A, PIK3CA, SMO, TERT promoter, and TRAF7). Patients with a radiation-induced meningioma or neurofibromatosis type 2 (NF2) were excluded from the study. Additionally, patient and tumor characteristics, including age, sex, radiological features, and tumor location, were retrospectively collected and evaluated. RESULTS: The study cohort consisted of 46 female and 16 male patients. Clinically significant driver mutations were detected in 58 patients (93.5%). The most commonly observed alteration was TRAF7 mutations (26, 41.9%), followed by AKT1E17K mutations (19, 30.6%). Both mutations were significantly associated with an anterolateral tumor location relative to the brainstem (p = 0.0078). NF2 mutations were present in 11 cases (17.7%) and were associated with posterior tumor location, in contrast to tumors with TRAF7 and AKT1E17K mutations. Other common mutations in FM meningiomas included POLR2A mutations (8, 12.9%; 6 POLR2AQ403K and 2 POLR2AH439_L440del), KLF4K409Q mutations (7, 11.3%), and PIK3CA mutations (4, 6.5%; 2 PIK3CAH1047R and 2 PIK3CAE545K). POLR2A and KLF4 mutations exclusively occurred in female patients and showed no significant association with specific tumor locations. All tumors harboring AKT1E17K and POLR2A mutations displayed meningothelial histology. Ten tumors exhibited intratumoral calcification, which was significantly more frequent in NF2-mutant compared with AKT1-mutant FM meningiomas (p = 0.047). CONCLUSIONS: These findings provide important insights into the molecular genetics and clinicopathological characteristics of FM meningiomas. The identification of specific genetic alterations associated with tumor location, volume, calcification, histology, and sex at diagnosis may have implications for personalized treatment strategies in the future.

Dental anomalies in cleft lip and/or palate children at age 10 - a retrospective review across three cleft centres: Part 1.

Introduction Children with oral clefts often present with dental anomalies which can impact function, aesthetics and complicate the patient's dental treatment and needs. An understanding of potential anomalies, along with early recognition and planning, is thus essential for effective care.Aim This paper is the first in a two-part three-centre series. This paper will assess the dental anomalies identified in 10-year-old patients attending three cleft centres in the UK.Method Retrospective review was undertaken of the clinical notes of 10-year-old patients attending South Wales (SW), Cleft NET East (CNE) and West Midlands (WM) cleft units, for their ten-year audit record appointment in 2016/2017.Results In total, 144 patients were reviewed (SW = 42; CNE = 52; WM = 50). Dental anomalies were recorded for 80.6% of patients (n = 116).Discussion The review gives insight into the dental complexities of UK oral cleft patients. These patients require specialist paediatric dental input and intensive preventive regimes.Conclusion Shared care between cleft team specialists and general dental practitioners is important when providing holistic care for cleft patients.

Associated medical conditions among 10-year-old children with oral clefts - a retrospective review across three cleft centres: Part 2.

Introduction In many cases, children with oral clefts present with accompanying medical conditions. These associated conditions can add complexity to the patient's dental management, both in terms of their treatment need and risk. Recognition and careful consideration of associated medical conditions is therefore crucial in providing safe and effective care for these patients.Aim This paper is the second in a two-part three-centre series. It investigates the prevalence of medical conditions affecting cleft lip and/or palate patients attending three cleft units within the UK.Method Retrospective review was undertaken within three cleft units: South Wales (SW), Cleft NET East (CNE) and West Midlands (WM). This was completed via assessment of the 10-year audit record appointment clinical notes for the year 2016/2017.Results In total, 144 cases were reviewed (SW = 42; CNE = 52; WM = 50). Of these, 38.9% of patients (n = 56) had associated medical conditions recorded.Discussion The review highlights the variety and impact of medical conditions affecting UK cleft patients providing insight into the consequent complexity of their dental care.Conclusion An awareness of cleft lip and/or palate patients' associated medical conditions is important for all health care professionals involved in their care. Indeed, understanding of the patient's medical needs by multidisciplinary cleft teams is essential for effective planning and completion of holistic care. Involvement of specialists in paediatric dentistry sharing care with general dental practitioners is vital in providing appropriate oral health care and preventive support.

Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas.

Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, the most common primary brain tumor, exhibit Hedgehog signaling activation in 6.5% of cases, triggered by recurrent mutations in pathway mediators such as SMO. In this study, we find 35.6% of meningiomas that lack previously known drivers acquired various types of somatic structural variations affecting chromosomes 2q35 and 7q36.3. These cases exhibit ectopic expression of Hedgehog ligands, IHH and SHH, respectively, resulting in Hedgehog signaling activation. Recurrent tandem duplications involving IHH permit de novo chromatin interactions between super-enhancers within DIRC3 and a locus containing IHH. Our work expands the landscape of meningioma molecular drivers and demonstrates enhancer hijacking of Hedgehog ligands as a route to activate this pathway  in neoplasia.

New physical insights: Formamide discharge decomposition and the role of fragments in the formation of large biomolecules.

In this work we present a time-resolved FTIR spectroscopic study on kinetics of atomic and molecular species, specifically CO, CN radical, N2, HCN and CO2 generated in a glow discharge of formamide-nitrogen-water mixture in a helium buffer gas. Radicals such as NH, CH and OH have been proven to be fundamental stones of subsequent chemical reactions having a crucial role in a prebiotic synthesis of large organic molecules. This work contains three main goals. Firstly, we present our time-resolved spectra of formamide decomposition products and discuss the mechanism of collisional excitations between specific species. Secondly, according to our time resolution, we demonstrate and explain the band shape of CO's first overtone and the energy transfer between excited nitrogen and CO, present in our spectra. Lastly, we present theoretical results for the non-LTE modelling of the spectra using bi-temperature approach and a 1D harmonic Franck-Condon approach for the multi-molecule spectra of the formamide decomposition process in the 1800-5600 cm-1 spectral range.

Genetic variation associated with condensate dysregulation in disease.

A multitude of cellular processes involve biomolecular condensates, which has led to the suggestion that diverse pathogenic mutations may dysregulate condensates. Although proof-of-concept studies have identified specific mutations that cause condensate dysregulation, the full scope of the pathological genetic variation that affects condensates is not yet known. Here, we comprehensively map pathogenic mutations to condensate-promoting protein features in putative condensate-forming proteins and find over 36,000 pathogenic mutations that plausibly contribute to condensate dysregulation in over 1,200 Mendelian diseases and 550 cancers. This resource captures mutations presently known to dysregulate condensates, and experimental tests confirm that additional pathological mutations do indeed affect condensate properties in cells. These findings suggest that condensate dysregulation may be a pervasive pathogenic mechanism underlying a broad spectrum of human diseases, provide a strategy to identify proteins and mutations involved in pathologically altered condensates, and serve as a foundation for mechanistic insights into disease and therapeutic hypotheses.

Clinical practice guidelines: Oral health care for children and adults living with epidermolysis bullosa.

BACKGROUND: Inherited epidermolysis bullosa (EB) is a genetic disorder characterized by skin fragility and unique oral features. AIMS: To provide (a) a complete review of the oral manifestations in those living with each type of inherited EB, (b) the current best practices for managing oral health care of people living with EB, (c) the current best practices on dental implant-based oral rehabilitation for patients with recessive dystrophic EB (RDEB), and (d) the current best practice for managing local anesthesia, principles of sedation, and general anesthesia for children and adults with EB undergoing dental treatment. METHODS: Systematic literature search, panel discussion including clinical experts and patient representatives from different centers around the world, external review, and guideline piloting. RESULTS: This article has been divided into five chapters: (i) general information on EB for the oral health care professional, (ii) systematic literature review on the oral manifestations of EB, (iii) oral health care and dental treatment for children and adults living with EB-clinical practice guidelines, (iv) dental implants in patients with RDEB-clinical practice guidelines, and (v) sedation and anesthesia for adults and children with EB undergoing dental treatment-clinical practice guidelines. Each chapter provides recommendations on the management of the different clinical procedures within dental practice, highlighting the importance of patient-clinician partnership, impact on quality of life, and the importance of follow-up appointments. Guidance on the use on nonadhesive wound care products and emollients to reduce friction during patient care is provided. CONCLUSIONS: Oral soft and hard tissue manifestations of inherited EB have unique patterns of involvement associated with each subtype of the condition. Understanding each subtype individually will help the professionals plan long-term treatment approaches.

Partitioning of cancer therapeutics in nuclear condensates.

The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this occurs through physicochemical properties independent of the drug target. This behavior was also observed in tumor cells, where drug partitioning influenced drug activity. Altering the properties of the condensate was found to affect the concentration and activity of drugs. These results suggest that selective partitioning and concentration of small molecules within condensates contributes to drug pharmacodynamics and that further understanding of this phenomenon may facilitate advances in disease therapy.

Understanding cleft lip and palate. 2: The first five years.

The second in a series on cleft lip and palate, this article outlines the diagnosis of these congenital anomalies, the problems that a child with a cleft lip and/or palate and their family may encounter in the first five years of life, and the multidisciplinary care needed. The input of individual members of the cleft team is described, including nurse specialists, speech and language therapists, paediatric dentists, ear, nose and throat surgeons, and audiologists.