Hurricane wind regimes for forests of North America.

Despite the ubiquity of tropical cyclones and their impacts on forests, little is known about how tropical cyclone regimes shape the ecology and evolution of tree species. We used a simple meteorological model (HURRECON) to estimate wind fields from hurricanes in the Western North Atlantic and Eastern North Pacific tropical cyclone basins from storms occurring between 1851 and 2022. We characterize how the intensity and frequency of hurricanes differ among geographically distinct hurricane regimes and define four hurricane regimes for North America (Continental, Inland, Coastal, and Fringe). Along this coastal-to-inland gradient, we found major differences in the frequency and intensity of hurricane wind regimes. The Fringe regime experiences category 1 winds relatively frequently [return period (RP) 25 y], whereas the Inland regime experiences category 1 winds very infrequently (RP ~3,000 y). We discuss how species traits related to tree windfirmness, such as mechanical properties and crown traits, may vary along hurricane regime gradients. Quantitative characterization of forest hurricane regimes provides a critical step for understanding the evolutionary and ecological role of hurricane regimes in wind-prone forests.

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.

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.

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.

Tropical cyclone winds and precipitation stimulate cone production in the masting species longleaf pine (Pinus palustris).

Many trees exhibit masting - where reproduction is temporally variable and synchronous over large areas. Several dominant masting species occur in tropical cyclone (TC)-prone regions, but it is unknown whether TCs correlate with mast seeding. We analyzed long-term data (1958-2022) to test the hypothesis that TCs influence cone production in longleaf pine (Pinus palustris). We integrate field observations, weather data, satellite imagery, and hurricane models to test whether TCs influence cone production via: increased precipitation; canopy density reduction; and/or mechanical stress from wind. Cone production was 31% higher 1 yr after hurricanes and 71% higher after 2 yr, before returning to baseline levels. Cyclone-associated precipitation was correlated with increased cone production in wet years and cone production increased after low-intensity winds (≤ 25 m s-1 ) but not with high-intensity winds (> 25 m s-1 ). Tropical cyclones may stimulate cone production via precipitation addition, but high-intensity winds may offset any gains. Our study is the first to support the direct influence of TCs on reproduction, suggesting a previously unknown environmental correlate of masting, which may occur in hurricane-prone forests world-wide.

Skin electronics from scalable fabrication of an intrinsically stretchable transistor array.

Skin-like electronics that can adhere seamlessly to human skin or within the body are highly desirable for applications such as health monitoring, medical treatment, medical implants and biological studies, and for technologies that include human-machine interfaces, soft robotics and augmented reality. Rendering such electronics soft and stretchable-like human skin-would make them more comfortable to wear, and, through increased contact area, would greatly enhance the fidelity of signals acquired from the skin. Structural engineering of rigid inorganic and organic devices has enabled circuit-level stretchability, but this requires sophisticated fabrication techniques and usually suffers from reduced densities of devices within an array. We reasoned that the desired parameters, such as higher mechanical deformability and robustness, improved skin compatibility and higher device density, could be provided by using intrinsically stretchable polymer materials instead. However, the production of intrinsically stretchable materials and devices is still largely in its infancy: such materials have been reported, but functional, intrinsically stretchable electronics have yet to be demonstrated owing to the lack of a scalable fabrication technology. Here we describe a fabrication process that enables high yield and uniformity from a variety of intrinsically stretchable electronic polymers. We demonstrate an intrinsically stretchable polymer transistor array with an unprecedented device density of 347 transistors per square centimetre. The transistors have an average charge-carrier mobility comparable to that of amorphous silicon, varying only slightly (within one order of magnitude) when subjected to 100 per cent strain for 1,000 cycles, without current-voltage hysteresis. Our transistor arrays thus constitute intrinsically stretchable skin electronics, and include an active matrix for sensory arrays, as well as analogue and digital circuit elements. Our process offers a general platform for incorporating other intrinsically stretchable polymer materials, enabling the fabrication of next-generation stretchable skin electronic devices.

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.

Treatment of Hip and Knee Periprosthetic Joint Infection Requires Extensive Administrative Work.

BACKGROUND: Treatment of periprosthetic joint infections (PJIs) typically requires more resource utilization than primary total joint arthroplasty. This study quantifies the amount of time spent in the electronic medical record (EMR) for patients who have PJI requiring surgical intervention. METHODS: A retrospective analysis of EMR activity for 165 hip and knee PJIs was performed to capture work during the preoperative and postoperative time periods. Independent sample t tests were conducted to compare total time based on procedure, age, insurance, health literacy, sex, race, and ethnicity. RESULTS: The EMR work performed by the orthopaedic team was 338.4 minutes (min) (SD 130.3), with 119.4 minutes (SD 62.8) occurring preoperatively and 219.0 minutes (SD 112.9) postoperatively. Preoperatively, the surgeon's work accounted for 35.7 minutes (SD 25.4), mid-level providers 21.3 minutes (SD 15.9), nurses 38.6 minutes (SD 36.8), and office staff 32.7 minutes (SD 29.9). Infectious disease colleagues independently performed 158.9 minutes (SD 108.5) of postoperative work. Overall, PJI of the knees required more postoperative work. Secondary analysis revealed that patients who have hip PJI and a body mass index <30 and patients <65 years of age required more work when compared to the PJI of heavier and older individuals. There was no difference in total work based on insurance, health literacy, race, or ethnicity. CONCLUSIONS: Over 8 hours of administrative work is required for surgical management of PJI. Surgeons alone performed 451% more work for PJI during the preoperative period (7.9 versus 35.7 min) compared to primary total joint arthroplasty. In efforts to provide best care for our sickest patients, much work is required perioperatively. This work is necessary to consider when assigning value and physician reimbursement.

Successful completion of orthodontic therapy in a patient with osteopetrosis: Case Report.

INTRODUCTION: Orthodontic therapy in patients with osteopetrosis (OP) of the jaws has typically been contraindicated owing to the presence of poorly perfused and extremely compact bone, and the potential risk for infection and osteomyelitis. As such, completed orthodontic cases in association with OP have rarely been published. PATIENT CONCERNS: A patient aged 14 years 6 months, with no known diagnosis of OP, sought orthodontic assessment for anterior crowding. CLINICAL FINDINGS: The patient exhibited a straight facial profile and increased mandibular facial height, competent lips, shallow mentolabial sulcus with mild mentalis strain, flat/reverse smile arc and wide buccal corridors on smiling. PRIMARY DIAGNOSIS: The patient had a Class I incisor relationship on Class I skeletal bases with bilateral Class I molars and Class II canine relationships. This was complicated by a crossbite involving the lateral incisors and a Bolton discrepancy due to small maxillary lateral incisors. A radiologic assessment revealed polyostotic OP of the oromaxillofacial complex. INTERVENTIONS: Treatment consisted of maxillary and mandibular fixed orthodontic therapy, bite turbos and elastics to level and align the dentition. Extractions of permanent teeth were not needed. OUTCOMES: At the conclusion of treatment, there was a slight left Class II malocclusion, with incomplete intercuspation on the left side due to tooth size discrepancy, possibly attributed to inadequate elastics compliance and the presence of osteopetrotic bone. The treatment was completed in 3 years, 1 year longer than anticipated. CONCLUSION: This report represents the second published account of a patient with OP successfully managed with comprehensive orthodontic care and without osseous complications. Obtaining cephalometric measurements on OP-affected patients may be imprecise owing to the presence of extremely dense bone and difficulty to identify bony landmarks. To reduce osteopetrotic sequelae, attending clinicians should consider reduced exertional orthodontic forces and closely monitor patients for adverse alveolar events.

Severe radiographic artifact created by a large fenestration of the skin and labial mucosa following placement of a plate piercing: a case report.

The presence of facial jewelry and medical devices within a radiographic field of view may promote the formation of artifacts that challenge diagnostic interpretation. The objective of this article is to describe a previously unreported radiographic anomaly produced by an oral piercing site below the lower lip. This unusual artifact masqueraded as a severe resorptive defect, dental caries, or cervical abfraction and occurred following removal of an extremely large labret below the lower lip and subsequent acquisition of a radiographic image. The radiolucency was ultimately attributed to an extensive aperture below the lower lip created by a series of sequentially larger soft tissue expanders. Clinicians should seek correlation of atypical radiographic presentations with soft tissue defects secondary to injury or intentional oral piercing.

Dental implant failure possibly attributed to embedded pencil graphite: first clinical report.

Implant failures have been associated with a diversity of etiologic processes, predominately arising from bone loss (peri-implantitis) due to inadequate maintenance of oral hygiene or excess luting agents. The aim of this article is to report a novel case of the apparent failure of a dental implant to undergo osseointegration in the presence of submerged pencil graphite. Practitioners are advised to carefully evaluate the clinical and radiographic site of a proposed implant for occult foreign substances. Embedded pencil graphite in the jawbone may promote a foreign body reaction and should be considered in the list of possible contributing factors to dental implant complications.

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.

Development and validation of a next-generation sequencing assay with open-access analysis software for detecting resistance-associated mutations in CMV.

Cytomegalovirus (CMV) resistance testing by targeted next-generation sequencing (NGS) allows for the simultaneous analysis of multiple genes. We developed and validated an amplicon-based Ion Torrent NGS assay to detect CMV resistance mutations in UL27, UL54, UL56, and UL97 and compared the results to standard Sanger sequencing. NGS primers were designed to generate 83 overlapping amplicons of four CMV genes (~10 kb encompassing 138 mutation sites). An open-access software plugin was developed to perform read alignment, call variants, and interpret drug resistance. Plasmids were tested to determine NGS error rate and minor variant limit of detection. NGS limit of detection was determined using the CMV WHO International Standard and quantified clinical specimens. Reproducibility was also assessed. After establishing quality control metrics, 185 patient specimens previously tested using Sanger were reanalyzed by NGS. The NGS assay had a low error rate (<0.05%) and high accuracy (95%) for detecting CMV-associated resistance mutations present at ≥5% in contrived mixed populations. Mutation sites were reproducibly sequenced with 40× coverage when plasma viral loads were ≥2.6 log IU/mL. NGS detected the same resistance-associated mutations identified by Sanger in 68/69 (98.6%) specimens. In 16 specimens, NGS detected 18 resistance mutations that Sanger failed to detect; 14 were low-frequency variants (<20%), and six would have changed the drug resistance interpretation. The NGS assay showed excellent agreement with Sanger and generated high-quality sequence from low viral load specimens. Additionally, the higher resolution and analytic sensitivity of NGS potentially enables earlier detection of antiviral resistance.

Progesterone Sporadically Induces Reactivation from Latency in Female Calves but Proficiently Stimulates Bovine Herpesvirus 1 Productive Infection.

Acute infection of the ocular, oral, or nasal cavity by bovine herpesvirus 1 (BoHV-1) culminates in lifelong latency in sensory neurons within trigeminal ganglia. The BoHV-1 latency reactivation cycle, including calves latently infected with commercially available modified live vaccines, can lead to reproductive complications, including abortions. Recent studies demonstrated progesterone stimulated BoHV-1 productive infection and sporadically induced reactivation from latency in male rabbits. The progesterone receptor (PR) and progesterone transactivate the immediate early transcription unit 1 (IEtu1) promoter and the infected cell protein 0 (bICP0) early promoter. These viral promoters drive expression of two viral transcriptional regulatory proteins (bICP0 and bICP4) that are crucial for productive infection. Based on these observations, we hypothesize that progesterone induces reactivation in a subset of calves latently infected with BoHV-1. These studies demonstrated progesterone was less efficient than dexamethasone at initiating reactivation from latency in female calves. Notably, heat stress correlated with enhancing the ability of progesterone to induce reactivation from latency. Previous studies demonstrated that heat stress activates the glucocorticoid receptor (GR), which suggested GR activation augments progesterone-mediated reactivation from latency. Additional studies revealed GR and PR cooperatively stimulated productive infection and synergistically transactivated the IEtu1 promoter when cultures were treated with dexamethasone. Mutating one or both GR binding sites in the IEtu1 promoter blocked transactivation. Collectively, these studies indicated that progesterone intermittently triggered reactivation from latency, and heat stress augmented reactivation from reactivation. Finally, these studies suggest progesterone enhances virus spread in tissues and cells where PR is abundantly expressed. IMPORTANCE Steroid hormone fluctuations are predicted to enhance or initiate bovine herpesvirus 1 (BoHV-1) replication and virus spread in cattle. For example, stress increases the incidence of BoHV-1 reactivation from latency in cattle, and the synthetic corticosteroid dexamethasone consistently induces reactivation from latency. The glucocorticoid receptor (GR) and dexamethasone stimulate key viral regulatory promoters and productive infection, in part because the viral genome contains numerous consensus GR-responsive elements (GREs). The progesterone receptor (PR) and GR belong to the type I nuclear hormone receptor family. PR and progesterone specifically bind to and transactivate viral promoters that contain GREs and stimulate BoHV-1 productive infection. Although progesterone did not induce reactivation from latency in female calves as efficiently as dexamethasone, heat stress enhanced progesterone-mediated reactivation from latency. Consequently, we predict that low levels of stressful stimuli can cooperate with progesterone to induce reactivation from latency or promote virus spread.

Whole grain consumption and risk of radiographic knee osteoarthritis: a prospective study from the Osteoarthritis Initiative.

OBJECTIVES: To assess the association of whole grain consumption with the risk of incident knee OA. MATERIAL AND METHODS: We followed 2846 participants in the Osteoarthritis Initiative ages 45-79 years. Participants were free from radiographic knee OA (Kellgren-Lawrence grade <2) in at least one knee at baseline. Dietary data from baseline were obtained using the Block Brief Food Frequency Questionnaire. We defined radiographic knee OA incidence as a Kellgren-Lawrence grade ≥2 during the subsequent 96 months. Cox proportional hazards models were used to assess the association between whole grain food intake and the risk of incident knee OA. RESULTS: During the 96 month follow-up, 518 participants (691 knees) developed incident radiographic knee OA. Higher total whole grain consumption was significantly associated with a lower knee OA risk [hazard ratio (HR)quartile 4vs1 = 0.66 (95% CI 0.52, 0.84), P for trend < 0.01] after adjusting for demographic and socio-economic factors, clinical factors and other dietary factors related to OA. Consistently, a significant inverse association of dark bread consumption with knee OA risk was observed [HRquartile 4vs1 = 0.68 (95% CI 0.53, 0.87), P for trend < 0.01). In addition, we observed a significant inverse association between higher cereal fibre intake and reduced knee OA risk [HRquartile 4vs1 = 0.61 (95% CI 0.46, 0.81), P for trend < 0.01). CONCLUSIONS: Our findings revealed a significant inverse association of whole grain consumption with knee OA risk. These findings provide evidence that eating a diet rich in whole grains may be a potential nutritional strategy to prevent knee OA.

Infectious complications associated with bronchial anastomotic dehiscence in lung transplant recipients.

INTRODUCTION: Bronchial anastomotic dehiscence (AD) is an uncommon complication following lung transplantation that carries significant morbidity and mortality. The objective of this study was to characterize fungal and bacterial infections in ADs, including whether infections following AD were associated with progression to bronchial stenosis. METHODS: This was a single-center study of 615 lung transplant recipients between 6/1/2015 and 12/31/2021. Airway complications were defined according to ISHLT consensus guidelines. RESULTS: 22 of the 615 recipients (3.6%) developed an AD. Bronchial ischemia or necrosis was common prior to dehiscence (68.1%). Fourteen (63.6%) recipients had bacterial airway infections, most commonly with Gram-negative rods, prior to dehiscence. Thirteen (59.1%) recipients had an associated pleural infection, most commonly with Candida species (30.8%). Post-dehiscence Aspergillus species were isolated in 4 recipients, 3 of which were de novo infections. Eleven had bacterial infections prior to dehiscence resolution, most commonly with Pseudomonas aeruginosa. Eleven recipients developed airway stenosis requiring dilation and/or stenting. Development of secondary infection prior to AD resolution was not associated with progression to stenosis (OR = .41, 95% CI = .05-3.30, p = .41). CONCLUSIONS: Gram-negative bacterial infections are common before and after AD. Pleural infection should be suspected in most cases. Infections prior to healing were not associated with subsequent development of airway stenosis.

Microsecond-timescale simulations suggest 5-HT-mediated preactivation of the 5-HT3A serotonin receptor.

Aided by efforts to improve their speed and efficiency, molecular dynamics (MD) simulations provide an increasingly powerful tool to study the structure-function relationship of pentameric ligand-gated ion channels (pLGICs). However, accurate reporting of the channel state and observation of allosteric regulation by agonist binding with MD remains difficult due to the timescales necessary to equilibrate pLGICs from their artificial and crystalized conformation to a more native, membrane-bound conformation in silico. Here, we perform multiple all-atom MD simulations of the homomeric 5-hydroxytryptamine 3A (5-HT3A) serotonin receptor for 15 to 20 µs to demonstrate that such timescales are critical to observe the equilibration of a pLGIC from its crystalized conformation to a membrane-bound conformation. These timescales, which are an order of magnitude longer than any previous simulation of 5-HT3A, allow us to observe the dynamic binding and unbinding of 5-hydroxytryptamine (5-HT) (i.e., serotonin) to the binding pocket located on the extracellular domain (ECD) and allosteric regulation of the transmembrane domain (TMD) from synergistic 5-HT binding. While these timescales are not long enough to observe complete activation of 5-HT3A, the allosteric regulation of ion gating elements by 5-HT binding is indicative of a preactive state, which provides insight into molecular mechanisms that regulate channel activation from a resting state. This mechanistic insight, enabled by microsecond-timescale MD simulations, will allow a careful examination of the regulation of pLGICs at a molecular level, expanding our understanding of their function and elucidating key structural motifs that can be targeted for therapeutic regulation.

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.

What every dentist needs to know about the use of artificial intelligence in dentistry.

Artificial intelligence (AI) is a division of computer science that allows machines to emulate human cognitive processes. In dentistry, AI is applied in clinical decision-making and can aid in detecting disease and predicting patterns based on existing data sets. AI can assist clinicians by quickly analyzing massive amounts of data to improve workflow, identify patterns of disease, provide risk assessment, and create individualized patient-centered treatment plans. AI has been shown to increase efficiency in the office by aiding in scheduling, tracking, and updating patient records to better organize patient data. The objective of this article is to outline the various applications of AI in different dental specialties. Applications range from business functions such as marketing, cyber security, and report writing to clinical uses such as lesion detection and surgical guidance. This review will also discuss some of the ethical considerations and drawbacks associated with implementing AI in the dental practice.

Modeling the membrane binding mechanism of a lipid transport protein Osh4 to single membranes.

All-atom (AA) molecular dynamics simulations are used to unravel the binding mechanism of yeast oxysterol binding protein (Osh4) to model membranes with varying anionic lipid concentration using AA and the highly mobile membrane mimetic (HMMM) representations. For certain protein-lipid interactions, an improved forcefield description is used (CUFIX) to accurately describe lipid-protein electrostatic interactions. Our detailed computational studies have identified a single, ß-crease oriented, membrane-bound conformation of Osh4 for all anionic membranes. The penetration of the PHE-239 residue below the membrane phosphate plane is the characteristic signature of the membrane-bound state of Osh4. As the phenylalanine loop anchors itself deeply in the membrane; the other regions of the Osh4, namely, ALPS motif, ß6- ß7 loop, ß14- ß15 loop, and ß16- ß17 loop, maximize their contact with the membrane. Furthermore, loose lipid packing and higher mobility of HMMM enable stronger association of the ALPS motif with the membrane lipids through its hydrophobic surface. After the HMMM is converted to AA and equilibrated, the binding is two to three times stronger compared with simulations started with the AA representation, yielding the major importance of the ALPS motif to binding. Quantitative estimation of binding energy revealed that the phenylalanine loop plays a crucial role in stable membrane attachment of Osh4 and contributes significantly toward overall binding process. The CUFIX parameters provide a more balanced picture of hydrophobic and electrostatic interactions between the protein and the membrane, which differs from our past work that showed salt bridges alone stabilized Osh4-membrane contact. Our study provides a comprehensive picture of the binding mechanism of Osh4 with model single membranes and, thus, understanding of the initial interactions is important for elucidating the biological function of this protein to shuttle lipids between organelles.