Investigation of the Effect of Peptide p5 Targeting CDK5-p25 Hyperactivity on Munc18-1 (P67) Regulating Neuronal Exocytosis Using Molecular Simulations.

Munc18-1 is an SM (sec1/munc-like) family protein involved in vesicle fusion and neuronal exocytosis. Munc18-1 is known to regulate the exocytosis process by binding with closed- and open-state conformations of Syntaxin1, a protein belonging to the SNARE family established to be central to the exocytosis process. Our previous work studied peptide p5 as a promising drug candidate for CDK5-p25 complex, an Alzheimer's disease (AD) pathological target. Experimental in vivo and in vitro studies suggest that Munc18-1 promotes p5 to selectively inhibit the CDK5-p25 complex without affecting the endogenous CDK5 activity, a characteristic of remarkable therapeutic implications. In this paper, we identify several binding modes of p5 with Munc18-1 that could potentially affect the Munc18-1 binding with SNARE proteins and lead to off-target effects on neuronal communication using molecular dynamics simulations. Recent studies indicate that disruption of Munc18-1 function not only disrupts neurotransmitter release but also results in neurodegeneration, exhibiting clinical resemblance to other neurodegenerative conditions such as AD, causing diagnostic and treatment challenges. We characterize such interactions between p5 and Munc18-1, define the corresponding pharmacophores, and provide guidance for the in vitro validation of our findings to improve therapeutic efficacy and safety of p5.

Florid follicular lymphoid hyperplasia of the palate: review of the literature and report of an illustrative case.

OBJECTIVE: The aim of this report was to review oral follicular lymphoid hyperplasia, with emphasis on palatal lesions. METHOD AND MATERIALS: A comprehensive search was performed on PubMed for case reports and case series of palatal follicular lymphoid hyperplasia published in the English language literature. Relevant data from collated articles was sought, including patient demographics, clinical manifestations, imaging modalities and findings, comorbidities, etiopathogenesis, lesional management, and lesional outcome. A new palatal case has also been provided to illustrate several features of this lesion. RESULTS: In total, 32 cases were assembled to establish clinicopathologic correlations, representing the largest aggregation of published cases. Most of the affected patients were at least 60 years old and with a decisive female predilection. The majority of lesions were ≤ 3 cm, appearing as normal color, purple-red or red, and varied from soft to firm. Notably, 32% of palatal follicular lymphoid hyperplasias were associated with denture wear, and lesional recurrence was recorded in 16% of cases. To date, none of the reported cases of palatal follicular lymphoid hyperplasia has undergone malignant transformation. CONCLUSIONS: Palatal follicular lymphoid hyperplasias often arise as a reactive process. Critical histopathologic and histochemical assessments are necessary to establish benignity. Postoperatively, clinicians should follow patients for at least 5 years for recurrence and remain vigilant for neoplastic change as several published accounts of non-oral follicular lymphoid hyperplasias have undergone malignant transformation, usually to lymphoma.

Chlorpromazine inhibits EAG1 channels by altering the coupling between the PAS, CNBH and pore domains.

EAG1 depolarization-activated potassium selective channels are important targets for treatment of cancer and neurological disorders. EAG1 channels are formed by a tetrameric subunit assembly with each subunit containing an N-terminal Per-Arnt-Sim (PAS) domain and C-terminal cyclic nucleotide-binding homology (CNBH) domain. The PAS and CNBH domains from adjacent subunits interact and form an intracellular tetrameric ring that regulates the EAG1 channel gating, including the movement of the voltage sensor domain (VSD) from closed to open states. Small molecule ligands can inhibit EAG1 channels by binding to their PAS domains. However, the allosteric pathways of this inhibition are not known. Here we show that chlorpromazine, a PAS domain small molecule binder, alters interactions between the PAS and CNBH domains and decreases the coupling between the intracellular tetrameric ring and the pore of the channel, while having little effect on the coupling between the PAS and VSD domains. In addition, chlorpromazine binding to the PAS domain did not alter Cole-Moore shift characteristic of EAG1 channels, further indicating that chlorpromazine has no effect on VSD movement from the deep closed to opened states. Our study provides a framework for understanding global pathways of EAG1 channel regulation by small molecule PAS domain binders.

Performance of AI chatbots on controversial topics in oral medicine, pathology, and radiology.

OBJECTIVES: In this study, we assessed 6 different artificial intelligence (AI) chatbots (Bing, GPT-3.5, GPT-4, Google Bard, Claude, Sage) responses to controversial and difficult questions in oral pathology, oral medicine, and oral radiology. STUDY DESIGN: The chatbots' answers were evaluated by board-certified specialists using a modified version of the global quality score on a 5-point Likert scale. The quality and validity of chatbot citations were evaluated. RESULTS: Claude had the highest mean score of 4.341 ± 0.582 for oral pathology and medicine. Bing had the lowest scores of 3.447 ± 0.566. In oral radiology, GPT-4 had the highest mean score of 3.621 ± 1.009 and Bing the lowest score of 2.379 ± 0.978. GPT-4 achieved the highest mean score of 4.066 ± 0.825 for performance across all disciplines. 82 out of 349 (23.50%) of generated citations from chatbots were fake. CONCLUSIONS: The most superior chatbot in providing high-quality information for controversial topics in various dental disciplines was GPT-4. Although the majority of chatbots performed well, it is suggested that developers of AI medical chatbots incorporate scientific citation authenticators to validate the outputted citations given the relatively high number of fabricated citations.

PC-PEP, a Comprehensive Daily Six-Month Home-Based Patient Empowerment Program Leads to Weight Loss in Men with Prostate Cancer: A Secondary Analysis of a Clinical Trial.

Background: The Prostate Cancer-Patient Empowerment Program (PC-PEP) is a six-month daily home-based program shown to improve mental health and urinary function. This secondary analysis explores weight loss in male PC-PEP participants. Methods: In a randomized clinical trial with 128 men undergoing curative prostate cancer (PC) treatment, 66 received 'early' PC-PEP, while 62 were assigned to the 'late' waitlist-control group, receiving 6 months of standard-of-care treatment followed by 6 months of PC-PEP. PC-PEP comprised 182 daily emails with video-based exercise and dietary (predominantly plant-based) education, live online events, and 30 min strength training routines (using body weight and elastic bands). Weight and height data were collected via online surveys (baseline, 6 months, and 12 months) including medical chart reviews. Adherence was tracked weekly. Results: No attrition or adverse events were reported. At 6 months, the early PC-PEP group experienced significant weight loss, averaging 2.7 kg (p < 0.001) compared to the waitlist-control group. Weight loss was noted in the late intervention group of PC-PEP, albeit less pronounced than in the early group. Early PC-PEP surgery patients lost on average 1.4 kg (SE = 0.65) from the trial's start to surgery day. High adherence to exercise and dietary recommendations was noted. Conclusions: PC-PEP led to significant weight loss in men undergoing curative prostate cancer treatment compared to standard-of-care.

Artificial intelligence for classification and detection of oral mucosa lesions on photographs: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to review and synthesize studies using artificial intelligence (AI) for classifying, detecting, or segmenting oral mucosal lesions on photographs. MATERIALS AND METHOD: Inclusion criteria were (1) studies employing AI to (2) classify, detect, or segment oral mucosa lesions, (3) on oral photographs of human subjects. Included studies were assessed for risk of bias using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). A PubMed, Scopus, Embase, Web of Science, IEEE, arXiv, medRxiv, and grey literature (Google Scholar) search was conducted until June 2023, without language limitation. RESULTS: After initial searching, 36 eligible studies (from 8734 identified records) were included. Based on QUADAS-2, only 7% of studies were at low risk of bias for all domains. Studies employed different AI models and reported a wide range of outcomes and metrics. The accuracy of AI for detecting oral mucosal lesions ranged from 74 to 100%, while that for clinicians un-aided by AI ranged from 61 to 98%. Pooled diagnostic odds ratio for studies which evaluated AI for diagnosing or discriminating potentially malignant lesions was 155 (95% confidence interval 23-1019), while that for cancerous lesions was 114 (59-221). CONCLUSIONS: AI may assist in oral mucosa lesion screening while the expected accuracy gains or further health benefits remain unclear so far. CLINICAL RELEVANCE: Artificial intelligence assists oral mucosa lesion screening and may foster more targeted testing and referral in the hands of non-specialist providers, for example. So far, it remains unclear if accuracy gains compared with specialized can be realized.

How Many Patients Qualify for Extended Oral Antibiotic Prophylaxis Infection Following Primary and Revision Hip and Knee Arthroplasties?

Extended oral antibiotic prophylaxis (EOAP) has been suggested to reduce rates of periprosthetic joint infection (PJI) postoperatively after total joint arthroplasty (TJA). The purpose of this multicenter study is to define how many TJA patients are considered high risk for developing PJI based on published EOAP criteria and determine whether this status is associated with socioeconomic or demographic factors. All primary and aseptic revision TJAs performed in 2019 at three academic medical centers were reviewed. High-risk status was defined based on prior published EOAP criteria. Area deprivation index (ADI) was calculated as a measure of socioeconomic status. Data were reported as means with standard deviation. Both overall and institutional differences were compared. Of the 2,511 patients (2,042 primary and 469 revision) in this cohort, 73.3% met criteria for high risk (primary: 72.9% [1,490] and revision: 74.6% [350]). Patient's race or age did not have a significant impact on risk designation; however, a larger proportion of high-risk patients were women (p = 0.002) and had higher Elixhauser scores (p < 0.001). The mean ADI for high-risk patients was higher (more disadvantaged) than for standard-risk patients (64.0 [20.8] vs. 59.4 [59.4]) (p < 0.001). Over 72% of primary and revision TJA patients at three medical centers met published criteria for EOAP. These patients were more often women, had more comorbidities, and lived in more disadvantaged areas. Our findings suggest that most patients qualify for EOAP, which may call for more stringent criteria on who would benefit extended antibiotic prophylaxis.

Diminutive compound odontoma in a child: a case report with emphasis on early detection.

The odontoma is regarded as a hamartomatous process of the jaws. Most are discovered as an incidental radiographic finding, averaging 15 mm in size. This report describes a case of a diminutive odontoma that was surgically removed before the onset of eruptive and pathologic consequences. A compilation of documented complications and syndromes associated with odontomas is also presented.

Molecular mechanism of EAG1 channel inhibition by imipramine binding to the PAS domain.

Ether-a-go-go (EAG) channels are key regulators of neuronal excitability and tumorigenesis. EAG channels contain an N-terminal Per-Arnt-Sim (PAS) domain that can regulate currents from EAG channels by binding small molecules. The molecular mechanism of this regulation is not clear. Using surface plasmon resonance and electrophysiology we show that a small molecule ligand imipramine can bind to the PAS domain of EAG1 channels and inhibit EAG1 currents via this binding. We further used a combination of molecular dynamics (MD) simulations, electrophysiology, and mutagenesis to investigate the molecular mechanism of EAG1 current inhibition by imipramine binding to the PAS domain. We found that Tyr71, located at the entrance to the PAS domain cavity, serves as a "gatekeeper" limiting access of imipramine to the cavity. MD simulations indicate that the hydrophobic electrostatic profile of the cavity facilitates imipramine binding and in silico mutations of hydrophobic cavity-lining residues to negatively charged glutamates decreased imipramine binding. Probing the PAS domain cavity-lining residues with site-directed mutagenesis, guided by MD simulations, identified D39 and R84 as residues essential for the EAG1 channel inhibition by imipramine binding to the PAS domain. Taken together, our study identified specific residues in the PAS domain that could increase or decrease EAG1 current inhibition by imipramine binding to the PAS domain. These findings should further the understanding of molecular mechanisms of EAG1 channel regulation by ligands and facilitate the development of therapeutic agents targeting these channels.

Detection of extracranial and intracranial calcified carotid artery atheromas in cone beam computed tomography using a deep learning convolutional neural network image segmentation approach.

OBJECTIVE: We leveraged an artificial intelligence deep-learning convolutional neural network (DL CNN) to detect calcified carotid artery atheromas (CCAAs) on cone beam computed tomography (CBCT) images. STUDY DESIGN: We obtained 137 full-volume CBCT scans with previously diagnosed CCAAs. The DL model was trained on 170 single axial CBCT slices, 90 with extracranial CCAAs and 80 with intracranial CCAAs. A board-certified oral and maxillofacial radiologist confirmed the presence of each CCAA. Transfer learning through a U-Net-based CNN architecture was utilized. Data allocation was 60% training, 10% validation, and 30% testing. We determined the accuracy of the DL model in detecting CCAA by calculating the mean training and validation accuracy and the area under the receiver operating characteristic curve (AUC). We reserved 5 randomly selected unseen full CBCT volumes for final testing. RESULTS: The mean training and validation accuracy of the model in detecting extracranial CCAAs was 92% and 82%, respectively, and the AUC was 0.84 with 1.0 sensitivity and 0.69 specificity. The mean training and validation accuracy in detecting intracranial CCAAs was 61% and 70%, respectively, and the AUC was 0.5 with 0.93 sensitivity and 0.08 specificity. Testing of full-volume scans yielded an AUC of 0.72 and 0.55 for extracranial and intracranial CCAAs, respectively. CONCLUSION: Our DL model showed excellent discrimination in detecting extracranial CCAAs on axial CBCT images and acceptable discrimination on full-volumes but poor discrimination in detecting intracranial CCAAs, for which further research is required.

Idiopathic bone cavity mimicking a botryoid odontogenic cyst: A rare radiographic presentation in an older adult.

OBJECTIVES: This report describes an unusual case of a multilocular idiopathic bone cavity (IBC) that presented as a botryoid odontogenic cyst situated between the mandibular lateral incisor and canine in an older adult. BACKGROUND: The IBC represents an intraosseous concavity that appears radiographically as a unilocular or multilocular radiolucent lesion found in various skeletal sites, including the jaw. Atypical cases of gnathic IBC have not been appreciated in the gerodontologic literature. MATERIALS AND METHODS: The teeth adjacent to the bony lesion had normal pulpal responses to cold. A full-thickness flap was elevated and provided a direct entry into a bony concavity, which was devoid of an epithelial lining and fluid. RESULTS: The lack of a cystic lining within the empty osseous lesion following surgical entry, concomitant with the vital pulpal status of the proximal teeth, led to a diagnosis of an IBC. The bony walls underwent curettage and copious irrigation prior to primary closure. A 10-month follow-up revealed partial evidence of osseous repair. The patient will continue to be monitored. CONCLUSION: Timely surgical intervention of central lesions of the jaws may improve clinical outcomes. Variants of the IBC should be included in the differential diagnosis of multilocular lesions, particularly in the geriatric population.

Rare nonsyndromic recurrent solitary gingival neurofibroma in an older adult.

BACKGROUND: Neurofibromas are benign peripheral nerve sheath tumors usually featured with neurofibromatosis type 1 syndrome. Recurrent gingival neurofibromas have been rarely reported in the periodontal literature, particularly affecting elderly patients. METHODS AND RESULTS: A 70-year-old man with a pale, rubbery, and painless thickening along the facial/buccal gingiva of the mandibular right canine and first premolar. Ten years prior, the patient had undergone excision of a neurofibroma within the same region. The patient denied a history of cutaneous disease or neurofibromatosis. Histopathologic and immunostaining of the excised lesion confirmed the diagnosis as a recurrent gingival neurofibroma. CONCLUSIONS: With cases of suspected recurrent neurofibroma, attending practitioners should consult with an oral pathologist whether the primary lesion had exhibited tumor cells to the surgical specimen margin. Preoperative use of a cone beam computed tomography scan may enhance determination of tumor depth. Clinicians should also carefully weigh the decision for conservative excision of gingival neurofibromas and greater risk of recurrence versus performing a somewhat wider extirpation and possible formation of a mucogingival defect. KEY POINTS: What are important clinical considerations when performing a gingival biopsy? Gingival neurofibromas may be associated with an increased risk for recurrence owing to decisions for tissue-sparing excision and prevention of a mucogingival defect; supplemental use of cone beam computed tomographic scans may provide greater appreciation of tumor depth. What is a reasonable length of time of postoperative assessment for gingival neurofibromas? Patients who have undergone surgical removal of a gingival neurofibroma should undergo yearly surveillance for at least 10 years. What is a key limitation to this case study? Preoperatively, attending clinicians should consult with an oral pathologist to ascertain whether a primary lesion had manifested tumor cells to the surgical margin. Conservative gingival resection of a neurofibroma may promote recurrence.

A Cadaver-based Comparison of Sleeve-guided Implant-drill and Dynamic Navigation Osteotomy and Root-end Resections.

INTRODUCTION: This study compared the accuracy and efficiency of fully guided static and dynamic computer-assisted surgical navigation techniques for osteotomy and root-end resection (RER). METHODS: Fifty roots from cadaver heads were divided into two groups: fully guided static computer-assisted endodontic microsurgery (FG sCAEMS) and dynamic computer-assisted endodontic microsurgery (dCAEMS) (all, n = 25). Cone-beam computed tomography scans were taken pre and postoperatively. The osteotomy and RER were planned virtually in the preoperative cone-beam computed tomography scan and guided using 3D-printed surgical guides in the FG sCAEMS and 3D-dynamic navigation system in the dCAEMS. The 2D and 3D deviations and angular deflection were calculated. The osteotomy volume, resected root length, and resection angle were measured. The osteotomy and RER time and the number of procedural mishaps were recorded. RESULTS: FG sCAEMS was as accurate as dCAEMS, with no difference in the 2D and 3D deviation values or angular deflection (P > .05). The osteotomy and RER time were shortened using FG sCAEMS (P < .05). The FG sCAEMS showed a greater number of incomplete RERs than dCAEMS. Osteotomy volume, RER angle, and root length resected were similar in both groups (P > .05). FG sCAEMS and dCAEMS were feasible for osteotomy and RER. CONCLUSIONS: Within the limitations of this cadaver-based study, FG sCAEMS was as accurate as dCAEMS. Both FG sCAEMS and dCAEMS were time-efficient for osteotomy and RER.

Diagnosis of vestibular schwannoma following an 11-year interval of head and neck manifestations: case report.

Vestibular schwannoma (VS) is a benign peripheral nerve sheath tumor involving the vestibulocochlear nerve. Affected patients typically experience a gradual emergence of episodic imbalance and unilateral hearing loss, tinnitus, and headache. Less often, VS may be associated with facial pain; ocular, otic, and taste disturbance; paresthesia of the tongue and face; and temporomandibular disorder-like presentations. There is limited information in the dental literature relating the myriad of oral and maxillofacial manifestations of VS. The objective of this article is to underscore the importance for dental clinicians to seek clinicopathologic correlations with VS-related symptomatology, potentially resulting in a timelier diagnosis and improved patient outcomes. To convey this clinical challenge, a detailed narrative of a 45-year-old patient with an 11-year delay in diagnosis has been reported. In addition, the typical radiographic appearance of an implanted cranial device placed following VS resection has been provided.

Recurrent peripheral odontogenic keratocyst: Review of the literature and presentation of a novel case initially masquerading as an atypical infected lateral periodontal cyst.

AIM: To review published cases and case series of the peripheral odontogenic keratocyst (POKC) of the gingiva, report an unusual presentation, and discuss lesional recurrence. MATERIALS AND METHODS: A search of the English language literature for gingival OKCs was conducted. The inclusion of new case yielded a database containing 29 affected patients. Clinical, surgical, radiographic, and histopathologic findings have been summarized. RESULTS: With available patient demographics, 62.5% were female and 37.5% were male, with an overall mean age at diagnosis of 53.8 years. There was near-equal lesional affinity for the jaws, of which 44.0% occurred in the posterior region, 32.0% anteriorly, and 24.0% overlapped these areas. Twenty-five percent of lesions had a normal color, 30.0% appeared yellow, 20.0% were white, and 10.0% were blue. The majority of lesions were < 1 cm and nearly 42% manifested exudation or fluctuance. Lesional pain was infrequent. Pressure resorption was recorded in 45.8% of cases. Most lesions were managed with conservative surgical modalities. Follow-up information was available in 16 primary cases, of which 5 recurred, signifying a 31.3% recurrence rate, including the featured case, which recurred twice. CONCLUSION: To reduce recurrence of a gingival OKC, supraperiosteal dissection is advocated. Further, it is advised to follow POKCs for 5-7 years postoperatively, remaining vigilant for subtle clinical manifestations of recurrence. Timely discovery and excision of a POKC of the gingiva may decrease the incidence of a mucogingival defect.

Slug, a Stress-Induced Transcription Factor, Stimulates Herpes Simplex Virus 1 Replication and Transactivates a cis-Regulatory Module within the VP16 Promoter.

Stress-mediated activation of the glucocorticoid receptor (GR) and specific stress-induced transcription factors stimulate herpes simplex virus 1 (HSV-1) productive infection, explant-induced reactivation, and immediate early (IE) promoters that drive expression of infected cell protein 0 (ICP0), ICP4, and ICP27. Several published studies concluded the virion tegument protein VP16, ICP0, and/or ICP4 drives early steps of reactivation from latency. Notably, VP16 protein expression was induced in trigeminal ganglionic neurons of Swiss Webster or C57BL/6J mice during early stages of stress-induced reactivation. If VP16 mediates reactivation, we hypothesized stress-induced cellular transcription factors would stimulate its expression. To address this hypothesis, we tested whether stress-induced transcription factors transactivate a VP16 cis-regulatory module (CRM) located upstream of the VP16 TATA box (-249 to -30). Initial studies revealed the VP16 CRM cis-activated a minimal promoter more efficiently in mouse neuroblastoma cells (Neuro-2A) than mouse fibroblasts (NIH-3T3). GR and Slug, a stress-induced transcription factor that binds enhancer boxes (E-boxes), were the only stress-induced transcription factors examined that transactivated the VP16 CRM construct. GR- and Slug-mediated transactivation was reduced to basal levels when the E-box, two 1/2 GR response elements (GREs), or NF-κB binding site was mutated. Previous studies revealed GR and Slug cooperatively transactivated the ICP4 CRM, but not ICP0 or ICP27. Silencing of Slug expression in Neuro-2A cells significantly reduced viral replication, indicating Slug-mediated transactivation of ICP4 and VP16 CRM activity correlates with enhanced viral replication and reactivation from latency. IMPORTANCE Herpes simplex virus 1 (HSV-1) establishes lifelong latency in several types of neurons. Periodically cellular stressors trigger reactivation from latency. Viral regulatory proteins are not abundantly expressed during latency, indicating cellular transcription factors mediate early stages of reactivation. Notably, the glucocorticoid receptor (GR) and certain stress-induced transcription factors transactivate cis-regulatory modules (CRMs) essential for expression of infected cell protein 0 (ICP0) and ICP4, key viral transcriptional regulatory proteins linked to triggering reactivation from latency. Virion protein 16 (VP16) specifically transactivates IE promoter and was also reported to mediate early stages of reactivation from latency. GR and Slug, a stress-induced enhancer box (E-box) binding protein, transactivate a minimal promoter downstream of VP16 CRM, and these transcription factors occupy VP16 CRM sequences in transfected cells. Notably, Slug stimulates viral replication in mouse neuroblastoma cells suggesting Slug, by virtue of transactivating VP16 and ICP4 CRM sequences, can trigger reactivation in certain neurons.

Comparison of a Novel Static Computer-aided Surgical and Freehand Techniques for Osteotomy and Root-end Resection.

INTRODUCTION: This study compared the accuracy and efficiency of a novel static computer-aided surgical technique using a 3-dimensional (3D)-printed surgical guide (3D-SG) with a fully guided drill protocol (3D-SG FG) to the freehand (FH) osteotomy and root-end resection (RER). METHODS: Forty-six roots from 2 cadaver heads were divided into 2 groups: 3D-SG FG (n = 23) and FH (n = 23). Cone-beam computed tomographic scans were taken preoperatively and postoperatively. The endodontic microsurgery was planned in Blue Sky Bio software, and the 3D-SG was designed and 3D printed. The osteotomy and RER were conducted using a guided twist drill diameter of 2 mm and an ascending tapered drill with diameters of 2.8/3.2, 3.2/3.6, 3.8/4.2, and 4.2 mm with respective guided drill guides. Two-dimensional and three-dimensional virtual deviations and angular deflection were calculated. Linear osteotomy measures and root resection angle were obtained. The osteotomy and RER time and the number of mishaps were recorded. RESULTS: Two-dimensional and three-dimensional accuracy deviations and angular deflection were lower in the 3D-SG FG protocol than in the FH technique (P < .05). The height, length, and depth of the osteotomy and root resection angle were less in the 3D-SG FG protocol than in the FH technique (P < .05). The osteotomy and RER time with the 3D-SG FG protocol were less than the FH method (P < .05). CONCLUSIONS: Within the limitations of this cadaver-based study using denuded maxillary and mandibular jaws, 3D-SG FG protocol showed higher accuracy than FH osteotomy and RER. Moreover, the 3D-SG FG drill protocol significantly reduced the surgical time.

Comparison of the Accuracy and Efficiency of a 3-Dimensional Dynamic Navigation System for Osteotomy and Root-end Resection Performed by Novice and Experienced Endodontists.

INTRODUCTION: The aim of the study is to investigate whether the 3-dimensional dynamic navigation system (3D-DNS) can improve experienced endodontists' (EEs') and novice endodontists' (NEs') accuracy and efficiency in osteotomy and root-end resection (RER) and to verify that the 3D-DNS enables NEs to perform osteotomy and RER as accurately and efficiently as EEs. METHODS: Seventy-six roots in cadaver heads were randomly divided into 4 groups: 3D-DNS-NE, 3D-DNS-EE, freehanded (FH)-NE, and FH-EE (all, n = 19). Cone-beam computed tomography scans were taken preoperatively and postoperatively. Osteotomy and RER were planned virtually in the X-guided software (X-Nav Technologies, Lansdale). Accuracy was calculated by measuring the 2-dimensional and 3D virtual deviations and angular deflection using superimposing software (X-Nav technologies). Efficiency was determined by the time of operation and the number of mishaps. RESULTS: Accuracy deviations were significantly fewer in the 3D-DNS-EE group than those in the FH-EE group (P < .05). We found less 2-dimensional and 3D accuracy deviations comparing the 3D-DNS-NE group to the FH-NE group (P < .05). The time required for osteotomy and RER with the 3D-DNS was ∼ ½ of that required for the FH method for both EEs and NEs (P < .05). We found no difference in the number of mishaps between the 3D-DNS and FH groups for EEs and NEs (P > .05). CONCLUSIONS: The 3D-DNS improved EEs' and NEs' accuracy and efficiency in osteotomy and RER. The NEs were as efficient as the EEs using the 3D-DNS. Notably, the 3D-DNS improved the NEs' accuracy compared to the FH method, but the 3D-DNS did not enable the NEs to perform osteotomy and RER as accurately as the EEs.

Computational Study of the Allosteric Effects of p5 on CDK5-p25 Hyperactivity as Alternative Inhibitory Mechanisms in Neurodegeneration.

The cyclin-dependent kinase (CDK5) forms a stable complex with its activator p25, leading to the hyperphosphorylation of tau proteins and to the formation of plaques and tangles that are considered to be one of the typical causes of Alzheimer's disease (AD). Hence, the pathological CDK5-p25 complex is a promising therapeutic target for AD. Small peptides, obtained from the truncation of CDK5 physiological activator p35, have shown promise in inhibiting the pathological complex effectively while also crossing the blood-brain barrier. One such small 24-residue peptide, p5, has shown selective inhibition toward the pathological complex in vivo. Our previous research focused on the characterization of a computationally predicted CDK5-p5 binding mode and of its pharmacophore, which was consistent with competitive inhibition. In continuation of our previous work, herein, we investigate four additional binding modes to explore other possible mechanisms of interaction between CDK5 and p5. The quantitative description of the pharmacophore is consistent with both competitive and allosteric p5-induced inhibition mechanisms of CDK5-p25 pathology. The gained insights can direct further in vivo/in vitro tests and help design small peptides, linear or cyclic, or peptidomimetic compounds as adjuvants of orthosteric inhibitors or as part of a cocktail of drugs with enhanced effectiveness and lower side effects.

Multiple miliary osteoma cutis, renal failure and secondary hyperparathyroidism in a geriatric patient.

INTRODUCTION: Miliary osteoma cutis (MOC) is a cutaneous disorder that develops in response to an ill-defined process or following acne vulgaris. Most cases present incidentally as small radiographic aggregations of normal bone within the cheeks. Infrequently, MOC has been reported with systemic disease, including renal failure. CASE PRESENTATION: An 82-year-old man presented with renal failure and secondary hyperparathyroidism. Intraoral radiographs displayed bilateral radiopacities. This is the first documented case of MOC synchronous with renal failure and secondary hyperparathyroidism in a geriatric patient. CONCLUSIONS: Patients with MOC and manifestations associated with nephropathy should undergo a comprehensive medical work-up and laboratory studies. Timely recognition of incidental radiographic findings may improve clinical outcomes.