Protein complex stoichiometry and expression dynamics of transcription factors modulate stem cell division.

Stem cells divide and differentiate to form all of the specialized cell types in a multicellular organism. In the Arabidopsis root, stem cells are maintained in an undifferentiated state by a less mitotically active population of cells called the quiescent center (QC). Determining how the QC regulates the surrounding stem cell initials, or what makes the QC fundamentally different from the actively dividing initials, is important for understanding how stem cell divisions are maintained. Here we gained insight into the differences between the QC and the cortex endodermis initials (CEI) by studying the mobile transcription factor SHORTROOT (SHR) and its binding partner SCARECROW (SCR). We constructed an ordinary differential equation model of SHR and SCR in the QC and CEI which incorporated the stoichiometry of the SHR-SCR complex as well as upstream transcriptional regulation of SHR and SCR. Our model prediction, coupled with experimental validation, showed that high levels of the SHR-SCR complex are associated with more CEI division but less QC division. Furthermore, our model prediction allowed us to propose the putative upstream SHR regulators SEUSS and WUSCHEL-RELATED HOMEOBOX 5 and to experimentally validate their roles in QC and CEI division. In addition, our model established the timing of QC and CEI division and suggests that SHR repression of QC division depends on formation of the SHR homodimer. Thus, our results support that SHR-SCR protein complex stoichiometry and regulation of SHR transcription modulate the division timing of two different specialized cell types in the root stem cell niche.

Partial Extraction Therapy: A Review of Human Clinical Studies.

Partial extraction therapy (PET) is a collective concept encompassing a group of surgical techniques including socket shield, root membrane, proximal shield, pontic shield, and root submergence. PET uses the patient's own root structure to maintain blood supply derived from the periodontal ligament complex to preserve the periodontium and peri-implant tissues during restorative and implant therapy. This review aims to summarize the current knowledge regarding PET techniques and present a comprehensive evaluation of human clinical studies in the literature. Two independent reviewers conducted electronic and manual searches until January 1, 2021, in the following electronic bibliographic databases: PubMed, EMBASE, and Dentistry & Oral Sciences Source. Gray literature was searched to identify additional candidates for potential inclusion. Articles were screened by a group of 4 reviewers using the Covidence software and synthesized. A systematic search of the literature yielded 5714 results. Sixty-four articles were selected for full-text assessment, of which 42 eligible studies were included in the review. Twelve studies were added to the synthesis after a manual search of the reference lists. A total of 54 studies were examined in this review. In sum, PET techniques offer several clinical advantages: (1) preservation of buccal bone postextraction and limitation of alveolar ridge resorption, (2) mitigation of the need for invasive ridge augmentation procedures, and (3) soft-tissue dimensional stability and high esthetic outcomes. Further randomized clinical studies with larger sample sizes are needed to improve the understanding of the long-term clinical outcomes of PET.

COVID-19's impact on private practice and academic dentistry in North America.

The COVID-19 pandemic is a major public health crisis for countries around the world. In response to this global outbreak, the World Health Organization declared a public health emergency of international concern. Dental professionals are especially at high risk of contracting the COVID-19 virus due to the unique nature of dentistry, more specifically, exposure to aerosols and droplets. When it comes to dental emergencies, it was crucial to maintain urgent dental care services operational to help reduce the burden on our healthcare system and hospitals already under pressure. The COVID-19 pandemic has significantly impacted how dentistry is practiced in North America in both the private practice and academic settings. This article shares the perspectives of dentists practicing in private practice and clinician-researchers in academic dental institutions. More specifically, we discuss about measures implemented to minimize risks of disease transmission, challenges in emergency dental care, impact on patients, as well as impact on the professional and personal lives of the dental team during the COVID-19 crisis.

Use of Artificial Intelligence in Dentistry: Current Clinical Trends and Research Advances.

The field of artificial intelligence (AI) has experienced spectacular development and growth over the past two decades. With recent progress in digitized data acquisition, machine learning and computing infrastructure, AI applications are expanding into areas that were previously thought to be reserved for human experts. When applied to medicine and dentistry, AI has tremendous potential to improve patient care and revolutionize the health care field. In dentistry, AI is being investigated for a variety of purposes, specifically identification of normal and abnormal structures, diagnosis of diseases and prediction of treatment outcomes. This review describes some current and future applications of AI in dentistry.

The impact of COVID-19 on dental education in North America-Where do we go next?

During the COVID-19 pandemic, the dental education community faced unprecedented challenges. In this commentary, we share the perspectives of faculty clinicians, residents and students in academic dental institutions in the United States and Canada. We discuss COVID-19's impact on various aspects of academic dentistry including patient care, education, research and raise key concerns regarding the future of dental education post-pandemic.

Biomarkers of the alcohol hangover state: Ethyl glucuronide (EtG) and ethyl sulfate (EtS).

INTRODUCTION: The aim of this study was to investigate the usefulness of ethyl glucuronide (EtG) and ethyl sulfate (EtS) as biomarkers of the hangover state. METHODS: Thirty-sixhealthy social drinkers participated in this study, being of naturalistic design. Eighteen participants experience regular hangovers (the hangover group), whereas the other 18 claim to not experience a hangover (the hangover-immune group). On a control day (alcohol-free) day and a post-alcohol day, urine EtG and EtS concentrations were determined and hangover severity assessed. RESULTS: Urinary EtG and EtS concentrations were significantly increased on post-alcohol day compared to the control day (p = .0001). Both EtG and EtS concentrations did not significantly correlate with the overall hangover score, nor with the estimated peak blood alcohol concentrations and number of alcoholic drinks. EtG correlated significantly only with the individual hangover symptom "headache" (p = .033; r = .403). No significant correlations were found with the EtG to EtS ratio. EtG and EtS concentrations significantly correlated with urine ethanol concentrations. CONCLUSIONS: Although urine EtG and EtS concentration did not significantly correlate to estimated peak blood alcohol concentrations or the number of alcoholic drinks consumed, a significant correlation was found with urine ethanol concentration. However, urine EtG and EtS concentrations did not significantly correlate with overall hangover severity.

Three- to 4-year follow-up of the reverse palatal pedicle graft for maxillary palatal recessions.

BACKGROUND: This study evaluates the long-term stability and clinical outcomes of the reverse palatal pedicle graft (RPPG) technique in treating maxillary molar palatal recessions over a 3 to 4-year follow-up period. METHODS: Three patients with palatal recession defects on maxillary molars were treated using the RPPG technique. Clinical parameters including recession depth, probing depth, and clinical attachment levels (CALs) were recorded at baseline, 2 months, and 3-4 years postoperatively. Healing outcomes, tissue perfusion, and soft tissue thickness were assessed through clinical examination, cone beam computed tomography (CBCT), and ultrasonography. RESULTS: All patients demonstrated significant CAL gain and partial root coverage. The RPPG technique resulted in significant improvements in attachment gain (41%-67%) and root coverage (44%-83%). In addition, a CBCT scan of one grafted site at a 4-year follow-up (Case 1) demonstrates a gain in soft tissue thickness and partial root coverage. Ultrasound imaging of another grafted site at a 4-year follow-up (Case 2) demonstrates a gain in soft tissue thickness and adequate graft perfusion. The outcomes suggest stable graft sites with some evidence of creeping attachment. CONCLUSION: The RPPG technique provides a viable option for treating maxillary molar palatal recessions, demonstrating promising long-term stability and clinical improvements. Further studies with larger sample sizes and frequent follow-ups are needed to better understand the dynamics of creeping attachment and refine clinical guidelines for palatal grafting. KEY POINTS: The reverse palatal pedicle graft (RPPG) is a surgical technique providing a viable solution for the treatment of maxillary molar palatal root coverage for a single recession site with 3-4 years of follow-up demonstrating a degree of predictability. Clinical indications for the application of the RPPG technique include severe palatal recession with little to no interproximal attachment loss (RT1 or RT2), palatal root sensitivity, and a sufficient amount of keratinized tissue on the palatal aspect of adjacent teeth. The main limitations of the application of the RPPG technique include its ability to treat only one isolated recession site, the inability for coronal advancement of the flap, and the quality and thickness of the autogenous graft being patient-dependent. PLAIN LANGUAGE SUMMARY: This study explores the reverse palatal pedicle graft (RPPG) technique, a method used to treat gum recession in the palate around the upper posterior teeth. The research followed three patients over a period of 3-4 years after they underwent the RPPG procedure. This technique involves using a piece of tissue from the roof of the mouth and repositioning it to cover the receded gum area. All patients showed significant improvement in gum attachment and coverage of the exposed roots. The grafts remained stable, and there was continued growth of the gum tissue, further covering the exposed roots over time. These promising results suggest that RPPG could be a reliable and effective option for treating severe gum recession on the roof of the mouth. However, further studies with larger patient groups are needed to confirm these findings and refine the technique.

Hydroxyethylamine-based inhibitors of BACE1: P1-P3 macrocyclization can improve potency, selectivity, and cell activity.

We describe a systematic study of how macrocyclization in the P1-P3 region of hydroxyethylamine-based inhibitors of ß-site amyloid precursor protein (APP)-cleaving enzyme (BACE1) modulates in vitro activity. This study reveals that in a number of instances macrocyclization of bis-terminal dienes leads to improved potency toward BACE1 and selectivity against cathepsin D (CatD), as well as greater amyloid ß-peptide (Aß)-lowering activity in HEK293T cells stably expressing APPSW. However, for several closely related analogs the benefits of macrocyclization are attenuated by the effects of other structural features in different regions of the molecules. X-ray crystal structures of three of these novel macrocyclic inhibitors bound to BACE1 revealed their binding conformations and interactions with the enzyme.

Regeneration of tissues of the oral complex: current clinical trends and research advances.

Regenerative therapy in oral health care is limited by both the body's natural capacity for regeneration and the materials and methods currently available. Research on various aspects of regenerative therapy, such as tissue engineering and stem cell and gene therapy, has produced promising results. Compelling advances, ranging from the discovery and characterization of stem cell populations in oral tissue to the engineering and transplantation of whole tooth structures, could result in exciting new treatment methods for clinicians in the near future. In this review, we discuss the limitations of natural healing and regeneration of various tissues of the oral complex, including teeth, periodontium and salivary glands, and summarize current treatment methods for tissue damage as well as research advances in oral tissue regeneration.

Multiple Subperiosteal Sling Sutures for Connective Tissue Graft Stabilization in the Treatment of Multiple Recession Defects Utilizing Subperiosteal Tunnels via VISTA and Intrasulcular Access.

This report describes the utilization of multiple subperiosteal sling (SPS) sutures to stabilize connective tissue grafts in the treatment of multiple recession defects using subperiosteal tunnels via vestibular and intrasulcular accesses. The SPS sutures engage only the graft and stabilize it against teeth inside the subperiosteal tunnel without engaging the overlying soft tissue, which is neither sutured nor coronally advanced. At sites with deep recessions, the graft is left exposed over the denuded root surfaces and allowed to epithelialize, which results in root coverage and increased attached keratinized tissue. Further controlled studies are required to investigate the predictability of this treatment approach.

Biomimicry and 3D-Printing of Mussel Adhesive Proteins for Regeneration of the Periodontium-A Review.

Innovation in the healthcare profession to solve complex human problems has always been emulated and based on solutions proven by nature. The conception of different biomimetic materials has allowed for extensive research that spans several fields, including biomechanics, material sciences, and microbiology. Due to the atypical characteristics of these biomaterials, dentistry can benefit from these applications in tissue engineering, regeneration, and replacement. This review highlights an overview of the application of different biomimetic biomaterials in dentistry and discusses the key biomaterials (hydroxyapatite, collagen, polymers) and biomimetic approaches (3D scaffolds, guided bone and tissue regeneration, bioadhesive gels) that have been researched to treat periodontal and peri-implant diseases in both natural dentition and dental implants. Following this, we focus on the recent novel application of mussel adhesive proteins (MAPs) and their appealing adhesive properties, in addition to their key chemical and structural properties that relate to the engineering, regeneration, and replacement of important anatomical structures in the periodontium, such as the periodontal ligament (PDL). We also outline the potential challenges in employing MAPs as a biomimetic biomaterial in dentistry based on the current evidence in the literature. This provides insight into the possible increased functional longevity of natural dentition that can be translated to implant dentistry in the near future. These strategies, paired with 3D printing and its clinical application in natural dentition and implant dentistry, develop the potential of a biomimetic approach to overcoming clinical problems in dentistry.

Partial Extraction Therapy (Part 2): Complication Management in Full-Arch Dental Implant Therapy.

Partial extraction therapy (PET) is a group of surgical techniques that preserve the periodontium and peri-implant tissues during restorative and implant therapy by conserving a portion of the patient's own root structure to maintain the blood supply, derived from the periodontal ligament complex. PET includes the socket shield technique (SST), proximal shield technique (PrST), pontic shield technique (PtST), and root submergence technique (RST). Although their clinical success and benefits have been demonstrated, several studies report possible complications. The focus of this article is to highlight management strategies for the most common complications associated with PET, including internal root fragment exposure, external root fragment exposure, and root fragment mobility.

Clinical outcomes of retention of the buccal root section combined with immediate implant placement: A systematic review of longitudinal studies.

INTRODUCTION: Immediate implant placement in conjunction with partial extraction therapy has been shown to result in functional osseo- and dento-integration with partial preservation of the periodontal ligament (PDL) in humans. Strategic buccal root retention for PDL preservation is a biologically driven procedure that maintains alveolar ridge dimensions and esthetics, while allowing for implant placement. The aim of this study was to conduct a systematic review of longitudinal clinical outcomes of PDL-mediated ridge preservation in conjunction with implant placement in adults, compared with conventional immediate implant placement with total extractions. The primary outcome for this study was marginal bone level (MBL) changes after strategic buccal root retention implant placement techniques. MATERIALS AND METHODS: To address a predefined PICOS question, a systematic search of randomized clinical trials and cohort studies with at least 10 participants per group and a minimum 12-month follow-up was conducted. A two-phase systematic selection strategy, data extraction, and risk of bias assessment, was performed independently and in duplicate. Randomized trials were quantitatively analyzed in a meta-analysis. RESULTS: Ten human studies fulfilled the predefined criteria and were included; three clinical trials and seven cohort studies, for a total of 506 patients and 587 implants. PDL-mediated implant placement of single-rooted periodontally healthy teeth was found to reduce marginal peri-implant bone loss and buccal plate changes as compared to conventional immediate implants across studies, while implant survival and success rates were comparable between the two procedures. A meta-analysis found that bone changes were significantly less when retention of the buccal root section was performed as compared to total extractions (standardized mean difference: [-4.53, -0.11]); the three clinical trials were, however, largely heterogeneous (I2 : 93.1%; Q = 28.98, p < 0.001). CONCLUSION: Strategic retention of the buccal root section has a benefit in terms of dimensional ridge stability over conventional immediate implantation when implemented in carefully selected cases of single-rooted teeth.

Structure guided P1' modifications of HEA derived ß-secretase inhibitors for the treatment of Alzheimer's disease.

The synthesis and SAR of a series of BACE-1 hydroxyethyl amine inhibitors containing substitutions on a spirocyclobutyl moiety is described. Selectivity against cathepsin D, a related aspartyl protease with potential off target toxicity, and improved microsomal stability is exemplified.

Targeting the Mitotic Kinesin KIF18A in Chromosomally Unstable Cancers: Hit Optimization Toward an In Vivo Chemical Probe.

Chromosomal instability (CIN) is a hallmark of cancer that results from errors in chromosome segregation during mitosis. Targeting of CIN-associated vulnerabilities is an emerging therapeutic strategy in drug development. KIF18A, a mitotic kinesin, has been shown to play a role in maintaining bipolar spindle integrity and promotes viability of CIN cancer cells. To explore the potential of KIF18A, a series of inhibitors was identified. Optimization of an initial hit led to the discovery of analogues that could be used as chemical probes to interrogate the role of KIF18A inhibition. Compounds 23 and 24 caused significant mitotic arrest in vivo, which was sustained for 24 h. This would be followed by cell death either in mitosis or in the subsequent interphase. Furthermore, photoaffinity labeling experiments reveal that this series of inhibitors binds at the interface of KIF18A and tubulin. This study represents the first disclosure of KIF18A inhibitors with in vivo activity.

A hybrid model connecting regulatory interactions with stem cell divisions in the root.

Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.

Risk assessment of labial bone perforation in the anterior mandibular region: a virtual immediate implant placement study.

BACKGROUND: This study investigated the prevalence of labial bone perforation (LBP) related to the associated anatomic factors in anterior mandibular region using a virtual immediate implant placement procedure. METHODS: Series qualified CBCT images of 149 participants (894 teeth) were selected to analyze the assigned anatomical parameters, including concavity depth, concavity angle, torque, and deep bone thickness. Four classes of crestal and radicular dentoalveolar bone phenotypes (CRDAPs) of mandibular anterior teeth were categorized according to the thickness of dentoalveolar bone at both crestal and radicular zones. Data were adjusted for categorical (gender and CRDAP) and continuous (age, cavity angle, cavity depth, and deep bone thickness) variables using a multivariable logistic regression analysis with generalized estimating equation method. RESULTS: The overall probability of LBP after virtual implant placement was 21.6%. There is statistically significant higher prevalence of LBP at canine (28.5%) and CRDAP class II (29.2%) regions (p < 0.001). After adjusting confounding variables, CRDAP class II and class IV regions are more likely to have LBP when compared with CRDAP class I (control) regions (p < 0.01). The risk of LBP at canine site is 6.31 times more likely than at the central incisor (control) (p < 0.01). CONCLUSIONS: Using a virtual immediate implant placement technique, the prevalence of LBP is significantly higher at the mandibular canine site and thin radicular dentoalveolar phenotype in the anterior mandibular region.

Socket Shield Technique Used in Conjunction With Immediate Implant Placement in the Anterior Maxilla: A Case Series.

INTRODUCTION: Bone remodeling after tooth extraction and immediate implant placement will occur nonetheless and as a result, additional hard and soft tissue augmentations are often necessary to compensate for the loss of alveolar ridge dimension. The socket shield (SS) technique has shown encouraging clinical results in maintaining original ridge morphology, and thus, may be used as an alternative protocol for the conventional immediate implant placement in the esthetic zone. CASE SERIES: The authors report three cases of SS technique used in conjunction with immediate implant placement in an anterior maxilla. The patients were followed for a period of 2 to 6 years, and the evolution of the soft and hard tissue surrounding the implants was documented. CONCLUSIONS: The SS technique produces virtually no change in the hard and soft tissue dimensions with relatively minimal invasive surgical interventions and shorter treatment time.

Effect of gingival phenotype on the maintenance of periodontal health: An American Academy of Periodontology best evidence review.

BACKGROUND: Gingival thickness, keratinized tissue width, and bone morphotype are three important parameters used to categorize periodontal phenotypes. These elements all play an important role in the maintenance of periodontal health. The aim of this review is to explore the importance of converting thin phenotype into a thick phenotype for periodontal health maintenance. METHODS: Three clinically relevant focused questions were defined to understand the role of gingival phenotype around teeth. 1) What are the factors affecting gingival phenotype (e.g., age, sex, dental arch, race, crown forms, etc.)? 2) Is there a difference between thin versus thick gingival phenotype in terms of gingival health? 3) Does the conversion of gingivae from a thin to thick gingival phenotype in sites without mucogingival defects help with periodontal health maintenance? RESULTS: Extensive electronic and manual literature search identified a total of 1,129 citations. After title, abstract, and full-text screenings, 30 articles were included in the present review. Twenty-five studies met the inclusion criteria and provided data for focused question 1. It was found that periodontal phenotype varies among different individuals and different areas of the mouth within the same individual. Asian individuals tend to have thinner gingival phenotype compared with white subjects. Eleven studies met the inclusion criteria for the focused question 2. Prevalence and severity of gingival recession was higher at the sites with thin gingiva compared with the sites with thicker gingiva. No studies provided data for focused question 3. CONCLUSIONS: Available evidence indicates that subjects with thin and narrow gingiva tend to have more gingival recession compared with those with thick and wide gingiva. Currently, there is no published evidence to support conversion of thin to thick gingival phenotype in sites without gingival recession or mucogingival deformity.

The Reverse Palatal Pedicle Graft for Maxillary Molar Palatal Recessions: Two Case Reports.

INTRODUCTION: Historically, the treatment of palatal recession was thought to be extremely challenging if not impossible due to the anatomy of the palate. A novel technique is presented for treating gingival recession on maxillary molars utilizing a rotated subepithelial connective tissue pedicle graft. The technique is designed to maximize perfusion to the graft as compared to a free graft CASE PRESENTATIONS: The authors present two cases in which the technique was utilized to achieve attachment gain and root coverage. The cases were followed for at least 2 months. CONCLUSIONS: More than 5 mm of attachment was gained and 55% to 60% root coverage achieved over recession defects on maxillary first molars. The following case reports demonstrate that the Reverse Palatal Pedicle Graft (RPPG) technique was successful in improving root coverage over maxillary palatal recession defects.