Whole-Exome Sequencing Identified Two Novel Pathogenic Mutations in the PTCH1 Gene in BCNS.

Basal cell nevus syndrome (BCNS, OMIM 109400) is a familial cancer syndrome characterized by the development of numerous basal cell cancers and various other developmental abnormalities, including epidermal cysts of the skin, calcified dural folds, keratocysts of the jaw, palmar and plantar pits, ovarian fibromas, medulloblastomas, lymphomesenteric cysts, and fetal rhabdomyomas. BCNS shows autosomal dominant inheritance and is caused by mutations in the patched 1 (PTCH1) gene and the suppressor of the fused homolog (SUFU) gene. In a few cases, variants of patched 2 (PTCH2) have been found in patients who met the criteria for BCNS. In an investigation of 11 Hungarian families who fulfilled the diagnostic criteria for BCNS, whole-exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA) identified two novel pathogenic variants (c.2994C>A; p.Cys998Ter and c.814_818del; p.Asn272SerfsTer11), one recently identified variant (c.1737_1745del p.Val580_Val582del), and three recurrent disease-causing variants of the PTCH1 gene with a diagnosis rate of 63.6%. Disease-causing variants were not found for the SUFU and PTCH2 genes. These applied methods could not fully elucidate the genetic background of all the BCNS cases that we investigated. To uncover the missing heritability of BCNS, whole-genome sequencing or an epigenetic approach might be considered in the future.

The Effect of Concentration, Temperature, and pH on the Formation of Hyaluronic Acid-Surfactant Nanohydrogels.

The assembly of colloidal hyaluronic acid (HyA, as a polysaccharide) based hydrogel particles in an aqueous medium is characterized in the present paper, with an emphasis on the particular case of nanohydrogels formed by surfactant-neutralized polysaccharide networks. The structural changes and particle formation process of polysaccharide- and cationic-surfactant-containing systems were induced by the charge neutralization ability and the hydrophobic interactions of cetyltrimethylammonium bromide (CTAB) under different conditions. Based on the rheological, light scattering, ζ-potential, turbidity, and charge titration measurements, it can be concluded that the preparation of the HyA-CTAB particles can be greatly controlled. The results indicate that more available negative charges can be detected on the polymer chain at smaller initial amounts of HyA (cHyA < 0.10 mg/mL), where a molecular solution can be formed. The change in the pH has a negligible effect on the formation process (particle aggregation appears at nCTAB/nHyA,monomer~1.0 in every case), while the temperature dependence of the critical micelle concentration (c.m.c.) of CTAB determines the complete neutralization of the forming nanohydrogels. The results of our measurements confirm that after the appearance of stable colloidal particles, a structural change and aggregation of the polymer particles take place, and finally the complete charge neutralization of the system occurs.

Translation and validation of the Hungarian version of the Orthognathic Quality of Life Questionnaire / Állcsontnövekedési zavarokra specifikus életminoség-kérdoív magyar nyelvu adaptálása

Introduction: Facial appearance undoubtedly has a strong influence on human life. While a harmonic and beautiful facial form may raise self-esteem, dentofacial deformities can lead not only to functional but also to aesthetic and psychosocial problems. Oral health-related quality of life is measured by several non-specific questionnaires but an adequate instrument for testing the quality of life in patients with dentofacial deformities in Hungarian is not yet available. Objective: Cross-cultural translation and validation of the most frequently used Orthognathic Quality of Life Questionnaire (OQLQ) into Hungarian. Method: The original 22-item OQLQ was translated from English to Hungarian (OQLQ-H) by a forward-backwards translation method. The questionnaire was filled out by patients who voluntarily agreed to take part in the study. Validity was evaluated according to the international guidelines. Reliability was evaluated by test-retest analysis. Internal consistency was measured by Cronbach's alpha. Results: OQLQ-H proved to be a reliable questionnaire with good validity and internal consistency. Conclusion: OQLQ-H is a reliable and valid measurement tool to assess dentofacial deformities in the Hungarian speaking population and therefore its use is recommended.

Detailed Calorimetric Analysis of Mixed Micelle Formation from Aqueous Binary Surfactants for Design of Nanoscale Drug Carriers.

While numerous papers have been published according to the binary surfactant mixtures, only a few articles provide deeper information on the composition dependence of the micellization, and even less work attempts to apply the enhanced feature of the mixed micelles. The most important parameter of the self-assembled surfactants is the critical micelle concentration (cmc), which quantifies the tendency to associate, and provides the Gibbs energy of micellization. Several techniques are known for determining the cmc, but the isothermal titration calorimetry (ITC) can be used to measure both cmc and enthalpy change (ΔmicH) accompanying micelle formation. Outcomes of our calorimetric investigations were evaluated using a self-developed routine for handling ITC data and the thermodynamic parameters of mixed micelle formation were obtained from the nonlinear modelling of temperature- and composition- dependent enthalpograms. In the investigated temperature and micelle mole fractions interval, we observed some intervals where the cmc is lower than the ideal mixing model predicted value. These equimolar binary surfactant mixtures showed higher solubilization ability for poorly water-soluble model drugs than their individual compounds. Thus, the rapid and fairly accurate calorimetric analysis of mixed micelles can lead to the successful design of a nanoscale drug carrier.

Genetic aspects of Gorlin‒Goltz syndrome / A Gorlin-Goltz-szindróma genetikai aspektusai.

Összefoglaló. A Gorlin-Goltz-szindróma - más néven naevoid basalsejtes carcinoma szindróma - egy ritka, viszont számos orvosi társszakmát érinto, rendkívül változatos megjelenésu és genetikailag is heterogén betegség. Bár a tudományos kutatások egyik kedvenc területe, az aránylag alacsony betegszám, valamint a genotípus és a fenotípus közötti, igen komplex összefüggések miatt a kórképrol meglévo ismereteink még nem teljesek. A témában megjelent nemzetközi és magyar nyelvu publikációk jelentos része esetközlésekre és a szindróma általános ismertetésére szorítkozik. A közlemény célja, hogy áttekintést adjon a szindróma genetikai vonatkozásairól. A nemzetközi és a magyar nyelvu szakirodalom áttanulmányozását végeztük. A naevoid basalsejtes carcinoma szindróma genetikai hátterének, az egyelore azonosítatlan örökletes tényezoknek pontos megismerése még várat magára. A genetikai vizsgálatok a szindróma pontosabb megértéséhez, könnyebb diagnosztizálásához, a pozitív családtervezéshez és a személyre szabott terápiákhoz is hozzájárulhatnak. Orv Hetil. 2020; 161(49): 2072-2077. Summary. Gorlin-Goltz syndrome, or nevoid basal cell carcinoma syndrome, is a rare disease that requires multidisciplinary approach in patient management. The disease is genetically heterogenous and has an extremely variable expressivity. Although the syndrome is in the focus of scientific research, our knowledge of it is still limited due to the relatively low number of recognised patients and the complexity of genotype-phenotype correlation. Several papers in this field have been published in the international and also in the Hungarian literature but most of these reports are single cases or small case series of families and outline general information about the disease. Authors aimed to review the literature of the syndrome and to report the genetic background and its role in the diagnosis and treatment. A review of the English and Hungarian literature was performed. The full genetic background of the syndrome is not yet discovered. Increasing the awareness of the syndrome, collecting and thoroughly analysing the medical records and performing genetic tests on the patients may lead to the better understanding of the disease; they may also help early diagnosis and treatment, positive family planning and may establish personalized medicine. Orv Hetil. 2020; 161(49): 2072-2077.

Principles of dental care of transplanted patients / Transzplantált betegek fogorvosi-szájsebészeti ellátásának alapelvei.

INTRODUCTION: The number of organ transplants is being on the rise. State-of-the-art immunosuppressive therapies and modern peri- and postoperative care have significantly increased life expectancy of transplanted patients, therefore, dentists and oral surgeons may encounter these patients more frequently. Although the number of successful transplants in Hungary has recently exceeded ten thousand; there is still no dental treatment protocol for these patients. AIM: The authors aimed to review and analyse the international literature about the perioperative dental care of transplanted patients based on good practice and evidence-based care protocols. MATERIAL AND METHOD: A review and comparative analysis of the English and Hungarian literature between 2010 and 2019 was conducted in relation to the objective pursued. RESULTS: The number of scientific papers in this topic is limited and their level of evidence is low. In our paper, the risk factors of transplantation and the cornerstones of perioperative, early and late postoperative dental management are described. Organ-specific considerations and possible oral manifestations of the applied medications are also presented. CONCLUSION: Lifelong administered immunosuppressive medications and the resulting artificially weakened immune system require increased attention from dentists and other healthcare professionals during patient aftercare. Close cooperation between the treating physician/surgeon and the dentist is essential to maintain patient safety. Moreover, inflammatory disorders may put the patients at increased risk, so maintaining good oral hygiene is essential. Regular dental check-ups, early detection and adequate therapy can be the cornerstones of long-term uncomplicated survival. Orv Hetil. 2020; 161(36): 1506-1513.

Cloud-Based Multicenter Data Collection and Epidemiologic Analysis of Bisphosphonate-Related Osteonecrosis of the Jaws in a Central European Population.

Objective: Bisphosphonate-related osteonecrosis of the jaws is considered to be a rare but severe complication of bisphosphonate therapy. To understand this condition better, data collection is essential. Although the number of scientific papers about this subject is large, to date only a few multicenter reports have been published. Study design: We present a novel cloud-based data collection system for the evaluation of the risk factors of bisphosphonate-related osteonecrosis of the jaws. Web-based questionnaire and database have been set up and made available to voluntary researchers and clinicians in oral and maxillofacial surgery in Hungary and Slovakia. Results: To date, fifteen colleagues from eight maxillofacial units have joined the study. Data of 180 patients have been recorded. Collected data were statistically analysed and evaluated from an epidemiological point of view. Conclusions: Authors consider cloud-based multicenter data collection a useful tool that allows for real-time collaboration between users, facilitates fast data entry and analysis, and thus considerably contributes to widening our knowledge of bisphosphonate-related osteonecrosis of the jaws.

[Current evidence-based approaches and international guidelines in primary and secondary prevention strategies of medication-related osteonecrosis of the jaws]. / Aktualitások a gyógyszer okozta állcsontelhalás primer és szekunder prevenciójának stratégiájában az evidenciák és a nemzetközi ajánlások tükrében.

Introduction: The presumably multifactorial pathomechanisms of medication-related osteonecrosis of the jaws have not been fully elucidated so far. Management of this rare but serious side effect is a real challenge and requires a multidisciplinary approach. Aim: The aim of the authors was to take stock of our present knowledge about the pathogenesis, risk factors, clinical manifestations and the possibilities of prevention and treatment in the medication-related osteonecrosis of the jaws. In addition, the available international guidelines are compared and the evidence-based, stage-specific conservative and adjuvant therapeutic approaches are also reviewed, having regard to special aspects of medical and dental care. Method: In the last 5 years - due to the increasing number of disorder-oriented database - the number of available systematic reviews, recommendations and meta-analyses has escalated significantly which we reviewed and compared. Results: Since the last Position Paper published by the taskforce of the American Association of Oral and Maxillofacial Surgeons, novel pharmacological groups with the potential to induce osteonecrosis have come in the clinical scope, further elaborating the nomenclature of the disease and further specifying patient groups. The sphere of patients at risk has broadened and novel patient groups (rheumatologic-osteological, immunosuppressed, transplanted or oncological patients treated with monoclonal antibody, known as 'target therapy') are expected to develop this serious side effect. Conclusion: Although a number of issues are still open regarding the treatment of the disorder, evidence-based, individualized, stage-adapted therapeutic approaches have replaced the previous empirical treatment. Orv Hetil. 2020; 161(6): 214-223.

[Transient diplopia and ophthalmoplegia following dental anaesthesia. Review of the literature and case report]. / Átmeneti kettos látás és szemizombénulás fogászati érzéstelenítést követoen.

Dental anaesthesia is one of the most frequently performed medical procedures. Although the frequency of ocular complications is low, these can be alarming and can potentially give rise to medicolegal issues. Dentists and oral surgeons should be well-informed of these adverse reactions. Ophthalmologists and emergency physicians might be required for appropriate care of these patients. Fortunately, most ocular complications related to dental anesthesia are transient. Differential diagnosis includes stroke and intracranial hemorrhage and so vital signs are to be closely monitored. The planned surgical procedure can be carried out once the patient is fully informed and gave consent. The psychological aspect of such unexpected complication must be managed appropriately. We report a case with diplopia and ophthalmoplegia of a reversible and temporary nature. We also include a literature review of ophthalmologic complications after intraoral local anaesthesia in this paper. Orv Hetil. 2018; 159(52): 2212-2216.

Severe root resorption of the upper central incisors as a consequence of playing the flute.

This study presents a case of severe root resorption of the maxillary central incisors in an 18-year-old woman who was referred for orthodontic treatment of irregular dental arches. A detailed history revealed that she used to play the block flute on an everyday basis during childhood. Against all warnings, she continued to firmly press her teeth into the mouthpiece of the instrument. Impressions of the upper central incisors were clearly visible on the instrument. Although it is well known that excessive occlusal forces can result in root resorption, to the authors' knowledge, this case involves one of the first reported occurrences of extensive root resorption that was most likely caused by playing a wind instrument during childhood.

[Surgery on virtual model and 3-dimensional printing of a surgical wafer for the correction of a severe mandibular asymmetry]. / Virtuális modell-mutét és az okklúziós lemez háromdimenziós nyomtatása súlyos mandibula aszimmetria esetében.

Correction of a severe facial asymmetry presents a challenge due to the geometric complexity of the dentition, the bony structures and the soft tissues. In most asymmetric cases two-jaw surgery is recommended. Manual model surgery is an essential part of treatment planning but it can be complicated, time-consuming and may contain potential errors. We present a case of a 26-year-old male with a severe right-sided hemimandibular elongation when computerized simulation surgery was performed instead of manual model surgery. High-resolution computer tomography scan was done following presurgical orthodontics and the stack images were reformatted into a three-dimensional structure. The symmetry of the maxilla was corrected via a virtual Le Fort I osteotomy with the help of a three-dimensional planning software. A virtual intermediate surgical wafer was designed and fabricated with a three-dimensional printer. Virtual bilateral sagittal split osteotomy was performed and the mandible was rotated into the correct position to visualize the movements of the osteotomized segments. Real surgery was accomplished according to the virtual plan. The splint fitted well. There is a significant improvement in the facial symmetry; the occlusion is good and stable. This case supports the usage of computer-aided surgical planning and three-dimensional rapid prototyping for the correction of facial asymmetries.

Correction of a severe facial asymmetry with computerized planning and with the use of a rapid prototyped surgical template: a case report/technique article.

Management of significant facial asymmetry presents a challenge due to the geometric complexity of the bony and other facial structures. Manual model surgery is an essential part of treatment planning but it can be complicated, time-consuming and may contain potential errors. Computer-aided surgery has revolutionized the correction of maxillofacial deformities. The aim of this study was to report a case of facial asymmetry when computerised simulation surgery was performed instead of manual model surgery and a virtually planned wafer splint was fabricated. A 26-year-old male was presented with a severe right-sided hemimandibular elongation. Following presurgical orthodontics high-resolution computer tomography scan was performed. The stack images were reformatted into a three-dimensional structure. Virtual Le Fort-I osteotomy was performed and the symmetry of the maxilla was corrected with the help of a three-dimensional planning software. A virtual intermediate surgical wafer was designed and produced with three-dimensional rapid prototyping technology. The mandible was rotated into the correct position following virtual bilateral sagittal split osteotomy to visualize the movements of the osteotomised mandibular segments. The two-jaw procedure was performed according to the virtual plan. The facial symmetry was improved significantly and stable occlusion was achieved. This complex case shows the advantages of computer-aided surgical planning and three-dimensional rapid prototyping for the correction of facial asymmetries.

Orthodontic screws to extrude impacted maxillary canines.

OBJECTIVE: The impaction of maxillary canines is a frequently encountered clinical problem in orthodontic practice. Patients' refusal to participate in long-term treatment or ankylosis of the impacted tooth result in various treatment difficulties. The aim of this study was to evaluate the possible role of mini-screws in the management of unerupted upper canines. PATIENTS AND METHODS: In a series of 63 consecutive patients (27 males and 36 females, age range 14-49 years, mean 22.7 years) with a total of 69 impacted maxillary canines, each impacted tooth was surgically exposed and an attachment bonded. An intraosseous screw with an endosseous body and intraoral neck section was inserted into the premolar-molar interradicular space. Following soft tissue healing, orthodontic traction was initiated. After correction of the canine angulation, the mini-screw was removed and conventional orthodontic therapy completed. RESULTS: Of the 69 canines, 61 (88.41%) were extruded successfully. In the 7 cases that failed, skeletal anchorage spared both patients and clinicians the disappointment of customary long-term, unsuccessful orthodontic therapy. In one patient, the mini-screw was removed because of inflammation and pain before initiating orthodontic traction. CONCLUSION: Our results demonstrate that mini-screw anchorage should be taken into consideration when extrusion of an impacted canine is planned.

Automated patient couch removal algorithm on CT images.

The current paper proposes a novel automated patient couch removal method on Computed Tomography (CT) images. Patient couch is often considered to be an unnecessary artifact especially when 3D rendered techniques are used. The method is based on measuring similarity between selected axial slices and the assumption that the bed object is constant on different slices. Due to the weight of the patient the couch could bend which is identifiable as sagittal movement on consecutive axial slices. Therefore the method focuses on finding this movement after an initial segmentation. According to initial validation performed on real medical data, our method is an effective tool to remove patient couch without user interaction.

[Skeletal anchorage: use of miniscrews for impacted maxillary canine management]. / Szkeletális elhorgonyzás: minicsavarok alkalmazása az impaktált szemfogak kezelésében.

Impaction of maxillary canines is a frequently encountered clinical problem. Patients' refusal to a long orthodontic treatment or ankylosis of the impacted tooth results in various treatment difficulties. The aim of this study was to evaluate the possible role of miniscrews in the management of impacted upper canines. In a series of 28 consecutive patients with a total of 31 impacted maxillary canines (12 men and 16 women aged from 14 to 63 years, mean 24 years), each impacted tooth was surgically exposed and an attachment was bonded. An intraosseous screw (1.5 mm in diameter and 8-10 mm long) with an endosseous body and intraoral neck section was inserted into the premolar-molar interradicular space. Following soft tissue healing, orthodontic traction was initiated. After correction of the angulation of the canine, the mini-screw was removed and traditional orthodontic therapy was completed. Twenty-seven canines were extruded successfully (87%), the duration of the orthodontic treatment with fixed appliances was decreased. In the 3 cases that failed due to ankylosis, the skeletal anchorage spared the patients and the clinicans the disappointment of a long-term unsuccessful traditional orthodontic treatment. In one patient, the mini-screw was removed because of inflammation and pain before the beginning of the orthodontic traction. This study shows that mini screw anchorage should be taken into consideration when extrusion of an impacted canine is planned.

[Osseointegration of dental implants after radiotherapy for oral cancer]. / Implantáció a szájüregi rák miatt sugárkezelésben részesült betegeken.

The goal of rehabilitation following radical surgery and radiotherapy for oral cancer is the restoration of oral functions and aesthetics. Osseointegrated implants improve prosthesis stability. Previous radiotherapy was originally considered a contraindication for implant placement. The aim of this study was to evaluate the survival of dental implants following radiotherapy. Nine oral cancer patients who had undergone radical surgery and radiotherapy were selected. A total of 23 implants were inserted. Twenty-one implants (91.3%) have been functioning without discomfort or infection. This study shows that osseointegrated implants should be considered part of the treatment plan for the rehabilitation of oral cancer patients after radiotherapy.

Closure of severe skeletal anterior open bite with zygomatic anchorage.

An open bite is commonly one of the main symptoms of an overall dentofacial deformity. Most anterior open-bite cases are characterized by excessive vertical development of the posterior maxilla. Intrusion of the overerupted molar teeth by traditional orthodontic methods is hardly possible; there is therefore no real alternative to a combined orthodontic and surgical approach. Skeletal anchorage has recently been proposed for the orthodontic movement of teeth. Titanium miniplates implanted in the zygomatic buttress area can serve as the absolute anchorage for maxillary molar intrusion. The aim of this study was to evaluate the use of skeletal anchorage for the closing of open-bite malocclusions. Seven patients with severe anterior open bites were selected, in all of whom the deformity was due to overeruption of the maxillary molars. Titanium miniplates were inserted bilaterally in the zygomatic buttress region and fixed with miniscrews. Elastic bands or coil springs were used to reduce excessive maxillary molar heights. In all cases, the anterior open bite improved significantly. The mean duration of active treatment was 6 months. No significant side effects were observed. Our results show that skeletal anterior open bites due to posterior maxillary dentoalveolar hyperplasia can be closed with intrusion of the upper molar teeth. This method is a safe, quick, and less expensive alternative to orthognathic surgery.

Crystal-storing histiocytosis associated with only one of two consecutive, but genetically unrelated B-cell lymphomas.

A localized crystal-storing histiocytosis (CSH) making the underlying marginal zone lymphoma (MZL) hardly discernible microscopically is described. Image analysis of the hyper electron dense crystals localized light microscopically in swollen histiocytic cells exhibited a major equatorial periodicity of 6.6 nm. Rarely, crystals of this type were detected within plasma cells, but were always surrounded by smooth membrane in contrast to Russell bodies. IgM/lambda restriction and VH3-21*02, DH4-17*01, JH4*02 gene usage were detected behind the lesion. Within 26 months, a genetically unrelated lymphoma of CD5-CD20-CD23-positive phenotype with a different VH1-24*01, DH2-21*02, JH2*01 heavy chain rearrangement, but with the same light chain gene usage, was identified without CSH. This might indicate that the unique condition responsible for the crystal formation is likely to rely on the sequence of the first clonally rearranged heavy chain exhibiting much higher CDRIII pI value (6.0) than the average.

Functional ABCG1 expression induces apoptosis in macrophages and other cell types.

The expression of the ATP-binding cassette transporter ABCG1 is greatly increased in macrophages by cholesterol loading via the activation of the nuclear receptor LXR. Several recent studies demonstrated that ABCG1 expression is associated with increased cholesterol efflux from macrophages to high-density lipoprotein, suggesting an atheroprotective role for this protein. Our present study uncovers an as yet not described cellular function of ABCG1. Here we demonstrate that elevated expression of human ABCG1 is associated with apoptotic cell death in macrophages and also in other cell types. We found that overexpression of the wild type protein results in phosphatidyl serine (PS) translocation, caspase 3 activation, and subsequent cell death, whereas neither the inactive mutant variant of ABCG1 (ABCG1K124M) nor the ABCG2 multidrug transporter had such effect. Induction of ABCG1 expression by LXR activation in Thp1 cells and in human monocyte-derived macrophages was accompanied by a significant increase in the number of apoptotic cells. Thyroxin and benzamil, previously identified inhibitors of ABCG1 function, selectively prevented ABCG1-promoted apoptosis in transfected cells as well as in LXR-induced macrophages. Collectively, our results suggest a causative relationship between ABCG1 function and apoptotic cell death, and may offer new insights into the role of ABCG1 in atherogenesis.