Dental abnormalities in rare genetic bone diseases: Literature review.

Currently, over 500 rare genetic bone disorders are identified. These diseases are often accompanied by dental abnormalities, which are sometimes the first clue for an early diagnosis. However, not many dentists are sufficiently familiar with phenotypic abnormalities and treatment approaches when they encounter patients with rare diseases. Such patients often need dental treatment but have difficulties in finding a dentist who can treat them appropriately. Herein we focus on major dental phenotypes and summarize their potential causes and mechanisms, if known. We discuss representative diseases, dental treatments, and their effect on the oral health of patients and on oral health-related quality of life. This review can serve as a starting point for dentists to contribute to early diagnosis and further investigate the best treatment options for patients with rare disorders, with the goal of optimizing treatment outcomes.

Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy.

BACKGROUND: Familial hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and is typically caused by mutations in genes encoding sarcomeric proteins that regulate cardiac contractility. HCM manifestations include left ventricular hypertrophy and heart failure, arrythmias, and sudden cardiac death. How dysregulated sarcomeric force production is sensed and leads to pathological remodeling remains poorly understood in HCM, thereby inhibiting the efficient development of new therapeutics. METHODS: Our discovery was based on insights from a severe phenotype of an individual with HCM and a second genetic alteration in a sarcomeric mechanosensing protein. We derived cardiomyocytes from patient-specific induced pluripotent stem cells and developed robust engineered heart tissues by seeding induced pluripotent stem cell-derived cardiomyocytes into a laser-cut scaffold possessing native cardiac fiber alignment to study human cardiac mechanobiology at both the cellular and tissue levels. Coupled with computational modeling for muscle contraction and rescue of disease phenotype by gene editing and pharmacological interventions, we have identified a new mechanotransduction pathway in HCM, shown to be essential in modulating the phenotypic expression of HCM in 5 families bearing distinct sarcomeric mutations. RESULTS: Enhanced actomyosin crossbridge formation caused by sarcomeric mutations in cardiac myosin heavy chain (MYH7) led to increased force generation, which, when coupled with slower twitch relaxation, destabilized the MLP (muscle LIM protein) stretch-sensing complex at the Z-disc. Subsequent reduction in the sarcomeric muscle LIM protein level caused disinhibition of calcineurin-nuclear factor of activated T-cells signaling, which promoted cardiac hypertrophy. We demonstrate that the common muscle LIM protein-W4R variant is an important modifier, exacerbating the phenotypic expression of HCM, but alone may not be a disease-causing mutation. By mitigating enhanced actomyosin crossbridge formation through either genetic or pharmacological means, we alleviated stress at the Z-disc, preventing the development of hypertrophy associated with sarcomeric mutations. CONCLUSIONS: Our studies have uncovered a novel biomechanical mechanism through which dysregulated sarcomeric force production is sensed and leads to pathological signaling, remodeling, and hypertrophic responses. Together, these establish the foundation for developing innovative mechanism-based treatments for HCM that stabilize the Z-disc MLP-mechanosensory complex.

Biodegradable nanofiber-based piezoelectric transducer.

Piezoelectric materials, a type of "smart" material that generates electricity while deforming and vice versa, have been used extensively for many important implantable medical devices such as sensors, transducers, and actuators. However, commonly utilized piezoelectric materials are either toxic or nondegradable. Thus, implanted devices employing these materials raise a significant concern in terms of safety issues and often require an invasive removal surgery, which can damage directly interfaced tissues/organs. Here, we present a strategy for materials processing, device assembly, and electronic integration to 1) create biodegradable and biocompatible piezoelectric PLLA [poly(l-lactic acid)] nanofibers with a highly controllable, efficient, and stable piezoelectric performance, and 2) demonstrate device applications of this nanomaterial, including a highly sensitive biodegradable pressure sensor for monitoring vital physiological pressures and a biodegradable ultrasonic transducer for blood-brain barrier opening that can be used to facilitate the delivery of drugs into the brain. These significant applications, which have not been achieved so far by conventional piezoelectric materials and bulk piezoelectric PLLA, demonstrate the PLLA nanofibers as a powerful material platform that offers a profound impact on various medical fields including drug delivery, tissue engineering, and implanted medical devices.

The use of electrodermal activity in pulpal diagnosis and dental pain assessment.

AIMS: To explore whether electrodermal activity (EDA) can serve as a complementary tool for pulpal diagnosis (Aim 1) and an objective metric to assess dental pain before and after local anaesthesia (Aim 2). METHODOLOGY: A total of 53 subjects (189 teeth) and 14 subjects (14 teeth) were recruited for Aim 1 and Aim 2, respectively. We recorded EDA using commercially available devices, PowerLab and Galvanic Skin Response (GSR) Amplifier, in conjunction with cold and electric pulp testing (EPT). Participants rated their level of sensation on a 0-10 visual analogue scale (VAS) after each test. We recorded EPT-stimulated EDA activity before and after the administration of local anaesthesia for participants who required root canal treatment (RCT) due to painful pulpitis. The raw data were converted to the time-varying index of sympathetic activity (TVSymp), a sensitive and specific parameter of EDA. Statistical analysis was performed using Python 3.6 and its Scikit-post hoc library. RESULTS: Electrodermal activity was upregulated by the stimuli of cold and EPT testing in the normal pulp. TVSymp signals were significantly increased in vital pulp compared to necrotic pulp by both cold test and EPT. Teeth that exhibited intensive sensitivity to cold with or without lingering pain had increased peak numbers of TVSymp than teeth with mild sensation to cold. Pre- and post-anaesthesia EDA activity and VAS scores were recorded in patients with painful pulpitis. Post-anaesthesia EDA signals were significantly lower compared to pre-anaesthesia levels. Approximately 71% of patients (10 of 14 patients) experienced no pain during treatment and reported VAS score of 0 or 1. The majority of patients (10 of 14) showed a reduction of TVSymp after the administration of anaesthesia. Two of three patients who experienced increased pain during RCT (post-treatment VAS > pre-treatment VAS) exhibited increased post-anaesthesia TVSymp. CONCLUSIONS: Our data show promising results for using EDA in pulpal diagnosis and for assessing dental pain. Whilst our testing was limited to subjects who had adequate communication skills, our future goal is to be able to use this technology to aid in the endodontic diagnosis of patients who have limited communication ability.

Design and Validation of a Multimodal Wearable Device for Simultaneous Collection of Electrocardiogram, Electromyogram, and Electrodermal Activity.

Bio-signals are being increasingly used for the assessment of pathophysiological conditions including pain, stress, fatigue, and anxiety. For some approaches, a single signal is not sufficient to provide a comprehensive diagnosis; however, there is a growing consensus that multimodal approaches allow higher sensitivity and specificity. For instance, in visceral pain subjects, the autonomic activation can be inferred using electrodermal activity (EDA) and heart rate variability derived from the electrocardiogram (ECG), but including the muscle activation detected from the surface electromyogram (sEMG) can better differentiate the disease that causes the pain. There is no wearable device commercially capable of collecting these three signals simultaneously. This paper presents the validation of a novel multimodal low profile wearable data acquisition device for the simultaneous collection of EDA, ECG, and sEMG signals. The device was validated by comparing its performance to laboratory-scale reference devices. N = 20 healthy subjects were recruited to participate in a four-stage study that exposed them to an array of cognitive, orthostatic, and muscular stimuli, ensuring the device is sensitive to a range of stressors. Time and frequency domain analyses for all three signals showed significant similarities between our device and the reference devices. Correlation of sEMG metrics ranged from 0.81 to 0.95 and EDA/ECG metrics showed few instances of significant difference in trends between our device and the references. With only minor observed differences, we demonstrated the ability of our device to collect EDA, sEMG, and ECG signals. This device will enable future practical and impactful advances in the field of chronic pain and stress measurement and can confidently be implemented in related studies.

Basic color categories in Mandarin Chinese revealed by cluster analysis.

Previous claims of the number of color categories and corresponding basic color terms in modern Mandarin Chinese remain irreconcilable, mainly due to the shortage in objectively evaluating the basicness of color terms with statistical significance. Therefore the present study applied k-means cluster analysis to investigate native Mandarin Chinese speakers' color naming data of 330 color chips similar to those used in World Color Survey. Results confirmed that there are 11 basic color categories among modern Mandarin speakers in Taiwan, one corresponding to each basic color term. Results also showed that observers overwhelmingly agreed in their use of Mandarin color terms, including those that had yielded ambiguous results in previous studies (gray, brown, pink, and orange). There is significant cross-language similarity when comparing the distribution of color categories in the World Color Survey chart with American English and Japanese data. The motif analysis and group mutual information analysis suggest that Mandarin color terms used in Taiwan describe very similar categories and are, hence, similarly precise in communicating color information as those in Japanese and American English. These results show that three languages of fundamentally different cultures and histories have very similar basic color terms.

Human Dendritic Cell-Derived Induced Pluripotent Stem Cell Lines Are Not Immunogenic.

Donor-specific induced pluripotent stem cells (iPSC) can be used to generate desired cell types, including naive immune effectors, for the treatment of different diseases. However, a greater understanding of the inherent immunogenicity of human iPSC and their cellular derivatives is needed for the development of safe and effective cell-replacement therapies, given that studies in mouse models claimed that the syngenic mouse iPSC lines can be immunogenic. We report the characterization of the innate and adaptive immune mechanisms in human iPSC lines derived from peripheral blood-derived dendritic cells using a nonintegrating RNA virus, Sendai virus. We show that these iPSC lines express mRNA of TLR molecules and the Ag-presentation pathway intermediates; however, these mRNA are not translated into functional proteins, and these iPSC lines do not induce TLR-mediated inflammatory cytokine responses or inflammasome activation. We also show that these iPSC lines do not activate T cells in an allogenic MLR; however, they express low levels of MHC class I molecules that can efficiently acquire antigenic peptides from their microenvironment and present them to Ag-specific T cells. In addition, we show that these iPSC lines can be efficiently differentiated into hematopoietic stem cell precursors, as well as APC, under appropriate culture conditions. Taken together, our data show that the dedifferentiation of human dendritic cells effectively shuts down their immunogenic pathways and implicates transcriptional and posttranscriptional mechanisms in this process.

Dietary phosphate supplement does not rescue skeletal phenotype in a mouse model for craniometaphyseal dysplasia.

BACKGROUND: Mutations in the human progressive ankylosis gene (ANKH; Mus musculus ortholog Ank) have been identified as cause for craniometaphyseal dysplasia (CMD), characterized by progressive thickening of craniofacial bones and flared metaphyses of long bones. We previously reported a knock-in (KI) mouse model (Ank KI/KI) for CMD and showed transiently lower serum phosphate (Pi) as well as significantly higher mRNA levels of fibroblast growth factor 23 (Fgf23) in Ank KI/KI mice. FGF23 is secreted by bone and acts in kidney to promote Pi wasting which leads to lower serum Pi levels. Here, we examined whether increasing the Pi level can partially rescue the CMD-like skeletal phenotype by feeding Ank +/+ and Ank KI/KI mice with high Pi (1.7 %) diet from birth for 6 weeks. We studied the Pi metabolism in Ank KI/KI mice and CMD patients by examining the Pi regulators FGF23 and parathyroid hormone (PTH). RESULTS: High Pi diet did not correct CMD-like features, including massive jawbone, increased endosteal and periosteal perimeters and extensive trabeculation of femurs in Ank KI/KI mice shown by computed microtomography (µCT). This unexpected negative result is, however, consistent with normal serum/plasma levels of the intact/active form of FGF23 and PTH in Ank KI/KI mice and in CMD patients. In addition, FGF23 protein expression was unexpectedly normal in Ank KI/KI femoral cortical bone as shown by immunohistochemistry despite increased mRNA levels for Fgf23. Renal expression of genes involved in the FGF23 bone-kidney axis, including mFgfr1, mKlotho, mNpt2a, mCyp24a1 and m1αOHase, were comparable between Ank +/+ and Ank KI/KI mice as shown by quantitative real-time PCR. Different from normal FGF23 and PTH, serum 25-hydroxyvitamin D was significantly lower in Ank KI/KI mice and vitamin D insufficiency was found in four out of seven CMD patients. CONCLUSIONS: Our data suggests that FGF23 signaling and Pi metabolism are not significantly affected in CMD and transiently low Pi level is not a major contributor to CMD.

Exploring Embodied Cognition and Brain Dynamics Under Multi-Tasks Target Detection in Immerse Projector-Based Augmented Reality (IPAR) Scenarios.

Embodied cognition explores the intricate interaction between the brain, body, and the surrounding environment. The advancement of mobile devices, such as immersive interactive computing and wireless electroencephalogram (EEG) devices, has presented new challenges and opportunities for studying embodied cognition. To address how mobile technology within immersive hybrid settings affects embodied cognition, we propose a target detection multitask incorporating mixed body movement interference and an environmental distraction light signal. We aim to investigate human embodied cognition in immersive projector-based augmented reality (IPAR) scenarios using wireless EEG technology. We recruited and engaged fifteen participants in four multitasking conditions: standing without distraction (SND), walking without distraction (WND), standing with distraction (SD), and walking with distraction (WD). We pre-processed the EEG data using Independent Component Analysis (ICA) to isolate brain sources and K-means clustering to categorize Independent Components (ICs). Following that, we conducted time-frequency and correlation analyses to identify neural dynamics changes associated with multitasking. Our findings reveal a decline in behavioral performance during multitasking activities. We also observed decreases in alpha and beta power in the frontal and motor cortex during standing target search tasks, decreases in theta power, and increases in alpha power in the occipital lobe during multitasking. We also noted perturbations in theta band power during distraction tasks. Notably, physical movement induced more significant fluctuations in the frontal and motor cortex than distractions from social environment light signals. Particularly in scenarios involving walking and multitasking, there was a noticeable reduction in beta suppression. Our study underscores the importance of brain-body collaboration in multitasking scenarios, where the simultaneous engagement of the body and brain in complex tasks highlights the dynamic nature of cognitive processes within the framework of embodied cognition. Furthermore, integrating immersive augmented reality technology into embodied cognition research enhances our understanding of the interplay between the body, environment, and cognitive functions, with profound implications for advancing human-computer interaction and elucidating cognitive dynamics in multitasking.

Skeletal abnormalities caused by a Connexin43R239Q mutation in a mouse model for autosomal recessive craniometaphyseal dysplasia.

Craniometaphyseal dysplasia (CMD), a rare craniotubular disorder, occurs in an autosomal dominant (AD) or autosomal recessive (AR) form. CMD is characterized by hyperostosis of craniofacial bones and flaring metaphyses of long bones. Many patients with CMD suffer from neurological symptoms. To date, the pathogenesis of CMD is not fully understood. Treatment is limited to decompression surgery. Here, we report a knock in (KI) mouse model for AR CMD carrying a R239Q mutation in CX43. Cx43KI/KI mice replicate many features of AR CMD in craniofacial and long bones. In contrast to Cx43+/+ littermates, Cx43KI/KI mice exhibit periosteal bone deposition and increased osteoclast (OC) numbers in the endosteum of long bones, leading to an expanded bone marrow cavity and increased cortical bone thickness. Although formation of Cx43+/+ and Cx43KI/KI resting OCs are comparable, on bone chips the actively resorbing Cx43KI/KI OCs resorb less bone. Cortical bones of Cx43KI/KI mice have an increase in degenerating osteocytes and empty lacunae. Osteocyte dendrite formation is decreased with reduced expression levels of Fgf23, Sost, Tnf-α, IL-1ß, Esr1, Esr2, and a lower Rankl/Opg ratio. Female Cx43KI/KI mice display a more severe phenotype. Sexual dimorphism in bone becomes more evident as mice age. Our data show that the CX43R239Q mutation results in mislocalization of CX43 protein and impairment of gap junction and hemichannel activity. Different from CX43 ablation mouse models, the CX43R239Q mutation leads to the AR CMD-like phenotype in Cx43KI/KI mice not only by loss-of-function but also via a not yet revealed dominant function.

ENPP1 enzyme replacement therapy improves ectopic calcification but does not rescue skeletal phenotype in a mouse model for craniometaphyseal dysplasia.

Craniometaphyseal dysplasia (CMD) is a rare genetic bone disorder, characterized by progressive thickening of craniofacial bones and flared metaphyses of long bones. Craniofacial hyperostosis leads to the obstruction of neural foramina and neurological symptoms such as facial palsy, blindness, deafness, or severe headache. Mutations in ANKH (mouse ortholog ANK), a transporter of small molecules such as citrate and ATP, are responsible for autosomal dominant CMD. Knock-in (KI) mice carrying an ANKF377del mutation (AnkKI/KI ) replicate many features of human CMD. Pyrophosphate (PPi) levels in plasma are significantly reduced in AnkKI/KI mice. PPi is a potent inhibitor of mineralization. To examine the extent to which restoration of circulating PPi levels may prevent the development of a CMD-like phenotype, we treated AnkKI/KI mice with the recombinant human ENPP1-Fc protein IMA2a. ENPP1 hydrolyzes ATP into AMP and PPi. Male and female Ank+/+ and AnkKI/KI mice (n ≥ 6/group) were subcutaneously injected with IMA2a or vehicle weekly for 12 wk, starting at the age of 1 wk. Plasma ENPP1 activity significantly increased in AnkKI/KI mice injected with IMA2a (Vehicle/IMA2a: 28.15 ± 1.65/482.7 ± 331.2 mOD/min; p <.01), which resulted in the successful restoration of plasma PPi levels (Ank+/+ /AnkKI/KI vehicle treatment/AnkKI/KI IMA2a: 0.94 ± 0.5/0.43 ± 0.2/1.29 ± 0.8 µM; p <.01). We examined the skeletal phenotype by X-Ray imaging and µCT. IMA2a treatment of AnkKI/KI mice did not significantly correct CMD features such as the abnormal shape of femurs, increased bone mass of mandibles, hyperostotic craniofacial bones, or the narrowed foramen magnum. However, µCT imaging showed ectopic calcification near basioccipital bones at the level of the foramen magnum and on joints of AnkKI/KI mice. Interestingly, IMA2a treatment significantly reduced the volume of calcified nodules at both sites. Our data demonstrate that IMA2a is sufficient to restore plasma PPi levels and reduce ectopic calcification but fails to rescue skeletal abnormalities in AnkKI/KI mice under our treatment conditions.

A Phe377del mutation in ANK leads to impaired osteoblastogenesis and osteoclastogenesis in a mouse model for craniometaphyseal dysplasia (CMD).

Craniometaphyseal dysplasia (CMD) is a rare genetic disorder with hyperostosis of craniofacial bones and widened metaphyses in long bones. Patients often suffer from neurological symptoms due to obstruction of cranial foramina. No proven treatment is available and the pathophysiology is largely unknown. A Phe377 (TTC(1130-1132)) deletion in exon 9 of the pyrophosphate (PPi) transporter ANK leads to CMD-like features in an Ank(KI/KI) mouse model. Here, we investigated the effects of CMD-mutant ANK on mineralization and bone mass at a cellular level. Ank(KI/KI) osteoblast cultures showed decreased mineral deposition. Expression of bone mineralization regulating genes Mmp13, Ocn, Osx and Phex was reduced in Ank(KI/KI) osteoblasts, while the Fgf23 mRNA level was highly elevated in Ank(KI/KI) calvarial and femoral bones. Since ANK is a known PPi transporter, we examined other regulators of Pi/PPi homeostasis Enpp1 and Tnap. Significantly increased ENPP1 activity may compensate for dysfunctional mutant ANK leading to comparable extracellular PPi levels in Ank(+/+) osteoblasts. Similar to Ank(KI/KI) bone marrow-derived macrophage cultures, peripheral blood cultures from CMD patients exhibited reduced osteoclastogenesis. Cell-autonomous effects in Ank(KI/KI) osteoclasts resulted in disrupted actin ring formation and cell fusion. In addition, Ank(KI/KI) osteoblasts failed to adequately support osteoclastogenesis. Increased bone mass could partially be rescued by bone marrow transplants supporting our hypothesis that reduced osteoclastogenesis contributes at least in part to hyperostosis. We conclude that the Phe377del mutation in ANK causes impaired osteoblastogenesis and osteoclastogenesis resulting in hypomineralization and a high bone mass phenotype.

A micro-computed tomography study of canal configuration of multiple-canalled mesiobuccal root of maxillary first molar.

OBJECTIVES: Detailed information of complex anatomical configuration of mesiobuccal (MB) root is essential for successful endodontic treatment in maxillary first molars. The aims of this study were to investigate the configuration types present in multiple-canalled MB roots of maxillary first molars using micro-computed tomography (µCT) and to evaluate whether further modification to current configuration classifications are needed for in-depth morphology study of MB root canal system. MATERIALS AND METHODS: One hundred and fifty-four extracted human maxillary first molar MB roots were scanned by µCT (Skyscan) and their canals were reconstructed by 3D modeling software. Root canal configurations were categorized according to the classifications proposed by Weine and Vertucci. Canal configurations that did not fit into both classifications were categorized as non-classifiable. RESULTS: One hundred and thirteen (73.4 %) MB roots had multiple canals. The most predominant canal configuration was Weine type III (two orifices and two foramens). Thirty-three (29.2 %) and 20 (17.7 %) MB roots had non-classifiable configuration types that could not be classified by the Weine and Vertucci classification, respectively. Three configurations (types 1-3, 2-3-2-3-2, and 2-3-4-3-2) were first reported in maxillary first molar MB roots. CONCLUSIONS: The present µCT study provided an in-depth analysis of canal configurations of the MB roots of maxillary first molar and suggests that additional modification of current configuration classifications may be needed to more accurately reflect the morphology configurations of MB roots. CLINICAL RELEVANCE: Clinicians should consider the complex canal configurations of the maxillary first molar MB roots during surgical or nonsurgical endodontic procedures.

Diversity and Suitability of the State-of-the-Art Wearable and Wireless EEG Systems Review.

Wireless electroencephalography (EEG) systems have been attracting increasing attention in recent times. Both the number of articles discussing wireless EEG and their proportion relative to general EEG publications have increased over years. These trends indicate that wireless EEG systems could be more accessible to researchers and the research community has recognized the potential of wireless EEG systems. To explore the development and diverse applications of wireless EEG systems, this review highlights the trends in wearable and wireless EEG systems over the past decade and compares the specifications and research applications of the major wireless systems marketed by 16 companies. For each product, five parameters (number of channels, sampling rate, cost, battery life, and resolution) were assessed for comparison. Currently, these wearable and portable wireless EEG systems have three main application areas: consumer, clinical, and research. To address this multitude of options, the article also discussed the thought process to find a suitable device that meets personalization and use cases specificities. These investigations suggest that low-price and convenience are key factors for consumer applications, wireless EEG systems with FDA or CE-certification may be more suitable for clinical settings, and devices that provide raw EEG data with high-density channels are important for laboratory research. This article presents an overview of the current state of the wireless EEG systems specifications and possible applications and serves as a guide point as it is expected that more influential and novel research will cyclically promote the development of such EEG systems.

Differentiating between stress- and EPT-induced electrodermal activity during dental examination.

Dental pain invokes the sympathetic nervous system, which can be measured by electrodermal activity (EDA). In the dental clinic, accurate quantification of pain is needed because it could enable optimized drug-dose treatments, thereby potentially reducing drug addiction. However, a confounding factor is that during pain there is also lingering residual stress, hence, both contribute to the EDA response. Therefore, we investigated whether EDA can differentiate stress from pain during dental examination. The use of electrical pulp test (EPT) is an ideal approach to tease out the dynamics of stress and mimic pain with lingering residual stress. Once the electrical sensation is felt and reaches a critical current threshold, the subject removes the probe from their tooth, hence, this stage of data represents largely EPT stimulus and the residual stress-induced EDA response is smaller. EPT was performed on necrotic and vital teeth in fifty-one subjects. We defined four different data groups of reactions based on each individual's EPT intensity level expectation based on the visual analog scale (VAS) of their baseline trial, as follows: mild stress, mild stress + EPT, strong stress, and strong stress + EPT. EDA-derived features exhibited significant difference between residual lingering stress + EPT groups and stress groups. We obtained 84.6% accuracy with 76.2% sensitivity and 86.8% specificity with multilayer perceptron in differentiating between pure-stress groups vs. stress + EPT groups. Moreover, EPT induced much greater EDA amplitude and faster response than stress. Our finding suggests that our machine learning approach can discriminate between stress and EPT stimulation in EDA signals.

Oculofaciocardiodental syndrome: a rare case and review of the literature.

Oculofaciocardiodental syndrome is a rare genetic disorder affecting ocular, facial, dental, and cardiac systems. The clinical diagnosis of oculofaciocardiodental syndrome can be challenging due to a wide variety of symptoms. Oculofaciocardiodental syndrome is found only in females due to its X-linked inheritance pattern and embryonic lethality for males. Radiculomegaly of canines is the most consistent finding in these patients. In this report we present a female patient with characteristic facial features, as well as a comprehensive overview of oculofaciocardiodental syndrome. Diagnosis of oculofaciocardiodental syndrome in this patient was verified by genetic analysis, during which we found a novel mutation in BCOR.

Tlr2/4-Mediated Hyperinflammation Promotes Cherubism-Like Jawbone Expansion in Sh3bp2 (P416R) Knockin Mice.

Cherubism (CBM), characterized by expansile jawbones with multilocular fibrocystic lesions, is caused by gain-of-function mutations in SH3 domain-binding protein 2 (SH3BP2; mouse orthologue Sh3bp2). Loss of jawbone and dental integrity significantly decrease the quality of life for affected children. Treatment for CBM is limited to multiple surgeries to correct facial deformities. Despite significant advances made with CBM knockin (KI) mouse models (Sh3bp2 KI/KI ), the activation mechanisms of CBM lesions remain unknown because mutant mice do not spontaneously develop expansile jawbones. We hypothesize that bony inflammation of an unknown cause triggers jawbone expansion in CBM. To introduce jawbone inflammation in a spatiotemporally controlled manner, we exposed pulp of the first right mandibular molar of 6-week-old Sh3bp2 +/+ , Sh3bp2 KI/+ , and Sh3bp2 KI/KI mice. Bacterial invasion from the exposed pulp into root canals led to apical periodontitis in wild-type and mutant mice. The pathogen-associated molecular patterns (PAMPs)-induced inflammation of alveolar bone resulted in jawbone expansion in Sh3bp2 KI/+ and Sh3bp2 KI/KI mice. CBM-like lesions developed exacerbated inflammation with increased neutrophil, macrophage, and osteoclast numbers. These lesions displayed excessive neutrophil extracellular traps (NETs) compared to Sh3bp2 +/+ mice. Expression levels of IL-1ß, IL-6, and TNF-α were increased in periapical lesions of Sh3bp2 +/+ , Sh3bp2 KI/+ , and Sh3bp2 KI/KI mice and also in plasma and the left untreated mandibles (with no pulp exposure) of Sh3bp2 KI/KI mice, suggesting a systemic upregulation. Ablation of Tlr2/4 signaling or depletion of neutrophils by Ly6G antibodies ameliorated jawbone expansion induced by PAMPs in Sh3bp2 KI/KI mice. In summary, successful induction of CBM-like lesions in jaws of CBM mice is important for studying initiating mechanisms of CBM and for testing potential therapies. Our findings further emphasize a critical role of host immunity in the development of apical periodontitis and the importance of maintaining oral health in CBM patients. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Inhibitory activities of omega-3 Fatty acids and traditional african remedies on keloid fibroblasts.

Keloids develop when scar tissue responds to skin trauma with proliferative fibrous growths that extend beyond the boundaries of the original wound and progress for several months or years. Keloids most frequently occur in individuals of indigenous sub-Saharan African origin. The etiology for keloids is still unknown and treatment can be problematic as patients respond differently to various treatment modalities. Keloids have a high rate of recurrence following surgical excision. Some West African patients claim to have had successful outcomes with traditional African remedies-boa constrictor oil (BCO) and shea butter-leading the authors to investigate their effects on cultured fibroblasts. The effects of emulsions of BCO, fish oil, isolated omega-3 fatty acids, and shea butter were tested in comparison to triamcinolone regarding inhibition of cell growth in keloid and control fibroblast cultures. In a series of controlled studies, it was observed that fish oil and BCO were more effective than triamcinolone, and that cis-5, 8, 11, 14, 17-eicosapentaenoic acid was more effective than -linolenic acid. While cell counts in control cultures continuously decreased over a period of 5 days, cell counts in keloid cultures consistently declined between day 1 and day 3, and then increased between day 3 and day 5 for all tested reagents except for fish oil. These results suggest that oils rich in omega-3 fatty acids may be effective in reducing actively proliferating keloid fibroblasts. Additional studies are warranted to investigate whether oils rich in omega-3 fatty acids offer effective and affordable treatment for some keloid patients, especially in the developing world.

Effect of display size on visual attention.

Attention plays an important role in the design of human-machine interfaces. However, current knowledge about attention is largely based on data obtained when using devices of moderate display size. With advancement in display technology comes the need for understanding attention behavior over a wider range of viewing sizes. The effect of display size on test participants' visual search performance was studied. The participants (N = 12) performed two types of visual search tasks, that is, parallel and serial search, under three display-size conditions (16 degrees, 32 degrees, and 60 degrees). Serial, but not parallel, search was affected by display size. In the serial task, mean reaction time for detecting a target increased with the display size.

Use of 3-dimensional-Printed Guide in Hemisection and Autotransplantation of a Fusion Tooth: A Case Report.

Three-dimensional (3D)-printed guides have been used in endodontics to prepare a conservative access, locate calcified or missing canals, and perform precisive osteotomy in apicoectomy. Here, we present the treatment of a fusion tooth by combining 3D printing technology and endodontic intervention in a 10-year-old patient. The bifid crown of a maxillary right lateral incisor #7 had caused esthetic concerns and malocclusion. Clinical and radiographic examinations showed that #7 is fused with a supernumerary tooth with 2 independent root canals. The fusion involved the entire crown and the coronal and middle roots. Because of financial constraints, a multidisciplinary approach involving endodontic, orthodontic, and prosthodontic treatment was excluded. We hemisectioned the tooth intraorally with a 3D-printed guide, extracted the supernumerary tooth, and transplanted tooth #7 to a position with improved esthetics and occlusion. A 3D-printed tooth replica was used to prepare the recipient site for autotransplantation. At the 6-month follow-up, tooth #7 was diagnosed with pulp necrosis and asymptomatic apical periodontitis. Root canal treatment of tooth #7 was completed, and osseous healing was observed 8 months later. The patient had no clinical symptoms and was satisfied with the outcome 14 months after hemisection and transplantation. The open space between teeth #7 and #8 was closed without orthodontic treatment. We present an alternative option to treat a fusion tooth in young patients who do not opt for other treatment options because of their stage of development or for socio-economic reasons. Techniques in modern endodontics, such as cone-beam computed tomographic imaging and 3D printing, should be adapted when it is beneficial to patients.